Pharma Middle East November 02-04, 2015 Dubai, UAE

Mohammed Meshal Almutairi, Abdulmajeed Farhan Alenazi, Ahmed Badah Alanazi, Yazen Talal Alenezi and Khalifa Ahmed Alenazi are had recently completed their graduation from Faculty of Medicine, Northern Borders University in 2015 and are currently pursuing Internship year in king fahad army forces hospital in Jeddah, KSA. They are looking forward to complete their post-graduation studies.

A new prenylated benzo-lactone (4,6-dihydroxy-5-methoxy-3-(1,2,3,4,5-pentahydroxypentyl)-2-benzofuran-1(3H)-one) was isolated from the acetone extracts of the rhizome of Cissus cornifolia and the structure of the compound was characterized using 1 and 2D NMR data. The antimicrobial activity of the compound was studied using the agar well method. The compound was active against 6 out of 10 tested clinical isolates of some microorganisms including S. aureus, S. typhi and C. albicans. The inhibition zones ranged between 17 and 25 mm against the microorganisms. The compound could serve as a lead for the development of more potent antimicrobial agent. To the best of our knowledge, this is the first report of the isolation and characterization as well as antimicrobial screening of the compound.

Aim of the study: Pentylenetetrazol (PTZ) is a commonly employed chemo-convulsant, used for screening drugs for anticonvulsant activity. The present study is aimed at investigating the differential effects of adenosine and the adenosine A1 agonist, N6-Cyclopentyladenosine (CPA) against seizures induced by Pentylenetetrazol (PTZ) Methods: This study was carried out by investigating the effect of pretreatment of rats with adenosine and CPA on Pentylenetetrazoleinduced seizures. Acute toxicity of PTZ in rats was studied by determination of median convulsive dose (CD50) of PTZ alone and after pretreatment of rats with each of adenosine and CPA. Results: Adenosine, when administered to rats i.p., in a dose of 1000 mg/kg 5 minutes prior to acute challenge with PTZ in a dose of 60 mg/kg, produced significant protection against PTZ-induced seizures. CPA, when administered i.p. to rats in a dose of 10 mg/kg 60 minutes prior to acute challenge with PTZ in a dose of 60 mg/kg, also showed significant protection against PTZ induced seizures. Conclusion: CPA significantly protected against seizures after acute PTZ administration and this indicates that the anticonvulsant effect of PTZ is via stimulation of A1 receptors.

Aim of the study: Theophylline, a methylxanthine derivative which was widely used in the treatment of asthma and bronchopulmonary obstructive diseases, is known to produce seizures which might be due to non-selective antagonistic effect on central adenosine receptors. This study provides an insight on the importance of how modulation of adenosine receptors might affect the neurological actions of theophylline and consequently might clarify a possible mechanistic approach to theophylline. Methods: This was carried out by studying the effect of pretreatment of rats with adenosine and its analogs on theophylline-induced seizures. Acute toxicity of theophylline in rats was studied by determination of median convulsive dose (CD50) of theophylline alone and after pretreatment of rats with adenosine and its analogs. The marginal dose of theophylline that elicits convulsions (i.e the least convulsive dose) and the serum level of theophylline at this dose were determined. Results: Pretreatment of rats with adenosine, 2-CADO, CPA and CPCA did not significantly offer protection against convulsions induced by acute challenge with theophylline in a dose of 200 mg/kg. Conclusion: Significant elevation of CD50 of theophylline after pretreatment of rats with adenosine and CPA is not conforming with the observation that adenosine and its analogs didn’t significantly offer protection against theophylline-induced seizures and this indicates that further investigations are needed to study role of adenosinergic system in theophylline-induced seizures.

Dr. Romany Helmy Thabet has completed his PhD at the age of 30 years from University of Assiut, Egypt. Now He is an assistant professor of Pharmacology, faculty of medicine, NBU, KSA. He has published several international papers in reputed journals. His Co-investigators are Nawaf Farhan Alrawili and Meshal Odhayb Alanazi who are now internship at Prince Sultan Military Medical City (PSMMC) in Riyadh, KSA.

Background & Aim: Rheumatoid Arthritis (RA) is an autoimmune disorder of unknown cause. It is a highly inflammatory polyarthritis disease often leading to joint destruction, deformity and loss of function. There is conflicting data about the effect of PDEIs on pathogenesis of RA. This work aims at investigation of the effect of rolipram as representative of PDEIs on signs, symptoms, histopathology and cytokines of Adjuvant-Induced Arthritis (AIA), a model of RA in rats that exhibit several pathological changes similar to those occurring in RA. Methods: In the present study, we used rat model of Adjuvant-Induced Arthrits (AIA), a model of RA in rats that exhibit several pathological changes similar to those occurring in RA in human, by sub-plantar administration of Freund’s adjuvant into hind paws of rats. Arthritis index, volume of hind paws edema, body weight ,rectal temperature and pain threshold to pressure on hind paws, were measured daily from day 0 until day 30 after adjuvant inoculation. At the end of the study, the animals were sacrificed and the blood was collected for measurement of serum levels of TNF-alpha and IL-10. To assess the secondary immune reaction, specimens of left ankle joint tissues were also examined for histopathology. Results: Rolipram therapy, either prophylactic or therapeutic, significantly leads to marked suppression of adjuvant arthritis in rats depending on the dose administered. The therapeutic efficacy of rolipram was evidenced by decreased arthritic scores, and hind paw volumes of arthritic rats. Hyperalgesia of adjuvant arthritic rats was significantly reduced in rolipram-treated animals compared to non-treated group. Prophylactic rolipram protocols have dramatic protective effect as evidenced by inhibition of inflammatory cellular infiltrate in synovium of arthritic rats, pannus formation and alleviation of the destruction of the articular cartilage. The present study demonstrated that prophylactic or therapeutic administration of rolipram did not alter significantly the serum level of TNF-α. Regarding IL-10, our study demonstrated a significantly augmenting effect of treating adjuvant arthritic rats with rolipram, from day 16 to day 25 after disease induction in a dose of 3 mg/kg/d given orally. Interestingly, the present work demonstrated that joint inflammation was significantly attenuated by DMSO treatment as evidenced by lower clinical scores and reduced paw swelling. Conclusion: The results presented in this study shows that rolipram, a PDE 4 inhibitor displayed an anti-inflammatory, anti-arthritic and anti-hyperalgesic actions in adjuvant arthritic rats in a dose-dependant manner. In conclusion, these findings suggest that rolipram may have therapeutic value for various autoimmune diseases such as rheumatoid arthritis.

Richie R Bhandare has completed his PhD from School of Pharmacy, Temple University, Philadelphia, USA in the area of Medicinal Chemistry. He is the Assistant Professor of Pharmaceutical Chemistry at Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management. He has published 6 papers in reputed journals, one book chapter and one US patent. He has been serving as an Reviewer for Medicinal Chemistry Research and Journal of Computer Science.

Histamine, a biogenic amine is involved in mediating numerous physiological effects through binding to its receptors. It belongs to GPCR superfamily. Currently, histamine receptors have taken attention as important targets for the treatment of several diseases and disorders. We have utilised priviledge structure based approach in the design of oxazolidinone based compounds as antiinflammatory agents. The small library represents a viable approach that could result in lead like compounds. Priviledge structure based approaches have been utilized in the literature with notable success in identification of high affinity ligands for GPCRs. The scaffold oxazolidinone may be considered a privileged structure because of its occurance in antibacterials, muscarinic ligands, etc. The objective of the present work was to investigate N3-substituted oxazolidinones as priviledge scaffold in the design of antiinflammatory agents. The study also investigated bioisosteric replacement of oxazlidinone using 1,3-benzodioxoles. The compounds were synthesized and purified using literature methods. The pharmacological activity was evaluated using standard animal models. Few compounds were chosen for their acute toxicity. The present data would be utilized for the generation of newer oxazolidinone based anti-inflammatory ligands.

Rofida A Saleh is a Demonstrator of Pharmacology & Toxicology at Faculty of Pharmacy, Cairo University. She completed her Bachelor’s degree. She is currently doing her Master’s degree in Pharmacology.

Alzheimer’s Disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. Recent accumulating evidences have demonstrated that disruption of neuronal insulin signaling is involved in the progression of AD. Moreover, it was proposed that saxagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor and an oral hypoglycemic might have neuroprotective properties. However, the signaling mechanisms underlying this action have not been fully delineated yet. Thus, the current study was directed to investigate the possible role of neuronal insulin signaling cascade and its interaction with cholinergic and GABAergic systems as potential mechanisms by which saxagliptin protects against scopolamine-induced Alzheimer’s like pathology in adult male rats. AD-related pathology was induced by a daily intraperitoneal injection of scopolamine at a dose of 3mg/kg for six weeks. Animals were orally administered saxagliptin, one hour before scopolamine injection, at a dose of 3mg/kg for six weeks. Saxagliptin mitigated scopolamine-induced cognitive and spatial memory deficits in rats. Such effects were accentuated by the associated increase in hippocampal acetylcholine. Furthermore a reduction in β-amyloid plaques, tau phosphorylation and its upstream glycogen synthase kinase 3-β (GSK-3β) was observed. Moreover, saxagliptin restored scopolamine-induced impairment of neuronal insulin. Collectively, our results suggest that saxagliptin can have a promising therapeutic effect in mitigating scopolamine-induced disruption of insulin signaling and other pathological aberrations in Alzheimer’s disease.

Doha E Ellakwa obtained her BSc degree in 2000 from Al-Alzhar University in Cairo, Egypt, and her PhD degree in Biochemistry in 2011 from Al-Alzhar University, in Cairo. She has published more than 5 papers in reputed journals. She showed that interleukin 28b as a predictor of sustained virological response in patients with chronic hepatitis C virus infection. She also showed the role of serum osteopontin level as a biomarker in hepatocellular carcinoma. Recently, she greatly contributed to detect the bcl2 polymorphism in patient with hepatocellular carcinoma.

Background: Diabetic Nephropathy (DN) is an extremely common complication of Diabetes Mellitus (DM) that affects more than 25% of all patients with type 2 DM; thus profoundly contributing to patient morbidity and mortality. Studies in human and experimental DN have shown that kidney macrophage accumulation is associated with the progression of diabetes, the development of renal injury, and the decline in renal function suggesting that it is an inflammatory-mediated disease. Monocyte Chemo-Attractant Protein-1 (MCP-1) is a CC chemokine, which plays an important role in the recruitment of monocytes and macrophages from the bloodstream to inflamed tissue. It has been demonstrated that MCP-1-mediated macrophage accumulation and activation is a critical mechanism in the development of DN. Aim: The present study aims to evaluate the diagnostic value of urinary MCP-1 as biomarkers for early detection of nephropathy in type 2 diabetic patients. Subjects & Methods: The current study was performed on sixty type 2 diabetic patients. Those patients were classified into three equal groups according to their Albumin Creatinine Ratio (ACR) including patients with normoalbuminuria (ACR<30 mg/g), patients with microalbuminuria (ACR 30-300 mg/g) and patients with macroalbuminuria (ACR>300 mg/g). Twenty apparently healthy subjects matching the same age and socioeconomic status were taken as a control group. Signed informed consent was obtained from each patient. Results: The mean urinary level of MCP-1 was significantly higher in all diabetic groups when compared to each other and when compared to control group. A significant positive correlation was found between urinary MCP-1 and urinary ACR, urine microalbumin and fasting plasma glucose and glycated hemoglobin in all diabetic groups. While a significant negative correlation was found between urinary MCP-1 and eGFR in all diabetic groups. The cut-off level for urinary MCP-1 was 148 g/ml (100% sensitivity and 100% specifity) for discriminating between the diabetic patients with and without nephropathy. Conclusion: The urinary MCP-1 is directly correlated with the severity of DN, which is an important indicator for the progression of albuminuria and closely linked to renal damage and the degree of glycemic control. Therefore, urinary MCP-1 might be of a diagnostic value as a marker for diagnosis of diabetic nephropathy in patients with type 2 diabetes.

Anzelle Delport has obtained her MSc Pharmaceutical Chemistry degree and is currently enrolled as a PhD student at the North-West University. Her doctoral is a combined study of Pharmaceutical Chemistry and Pharmacology which has given her opportunity to obtain skills in both disciplines. She won the Academy of Pharmaceutical Sciences of the Pharmaceutical Society of South Africa’s Young Scientist podium presentation award in 2013 and published an article in 2014. Her research is based on methylene blue and synthesis of new methylene blue derivatives for treatment in neurodegenerative and neurological diseases. She is currently an assistant-supervisor to a postgraduate student.

Methylene blue (MB) is a heterocyclic aromatic chemical compound composed of the phenothiazine nucleus and is not only the first synthetic drug against malaria but also the first synthetic compound to be used therapeutically. In recent years the focus has shifted to MB as an antimalarial agent and as potential treatment of neurodegenerative disorders such as Alzheimer’s disease. Of interest to us are reports that MB possesses antidepressant and anxiolytic activities in pre-clinical models and has shown promise in clinical trials for bipolar disorder. MB is a noteworthy inhibitor of monoamine oxidase A (MAO-A), which is a well-established mechanism of antidepressant action. MB is also recognized as a non-selective inhibitor of nitric oxide synthase (NOS) and guanylate cyclase, and dysfunction of the NO-cGMP cascade is strongly linked to the neurobiology of depression. Since the inhibition of NOS and guanylate cyclase has been associated with an antidepressant response, this pharmacological effect of MB may contribute significantly to its antidepressant activity. The aim of this study was to synthesize novel symmetrical and asymmetrical MB analogues by employing improved synthetic routes and to evaluate the effects of the resulting structural changes on MAO-A and MAO-B inhibition.

Nasir Tajuddeen has completed his MSc in Organic Chemistry at Ahmadu Bello University Zaria. He is currently pursuing his PhD in the same University. His focus is exploring medicinal plants for bioactive molecules that can be adopted as new therapeutic agents or that can serve as lead in drug discovery. He has published 5 papers in reputed journals.

A new flavonoid, 2-(3,5-dihydroxy-4-methoxy-phenyl)-3,5-dihydroxy-8,8-dimethyl-2,3-dihydro-8H-pyrano[3,2]chromen-4-one together with previously reported epicatechin were isolated from the ethyl acetate soluble fraction of the methanol extract of the stem bark of Commiphora pedunculata. The structures of these compounds were elucidated based on extensive analysis of their spectral data, including 1 and 2D NMR. The compounds were active against nine out of twelve tested microorganisms including a resistant strain; vancomycin resistant Entrococci (VRE), Escherichia coli, Staphylococcus aureus and Candida albicans. The zones of inhibition ranged between 22 and 34 mm against the microorganisms. The Minimum Inhibitory Concentration (MIC) was as low as 6.25 μg/mL against Shigella dysentriae, Bacillus cereus and Staphylococcus aureus while the Minimum Bactericidal Concentration (MBC) was as low as 50 μg/mL against Pseudomonas aeruginosa, VRE and Candida albicans. This is the first report of the isolation of the compound.

Nesrin Gökhan-Kelekçi has completed her PhD in Pharmaceutical Chemistry at Hacettepe University and Postdoctoral studies from Braunschweig University of Technology and Kings College London. She is the Vice Dean of Faculty of Pharmacy of Hacettepe University. She has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of some journals.

In the five membered nitrogen containing heterocyclic family, 2-pyrazoline could be encountered as the most promising scaffold for antidepressant activity. Recently, this nucleus was endowed with remarkable attention in the inhibition of monoamine oxidase A (MAO-A), which is considered as the effective target for the management of depressive disorders. The literature survey revealed that the substitutions of 2-pyrazoline nucleus preferably at the N1, C3, and C5 positions showed remarkable effect in the central nervous system. Prasad et al. reported that the compounds possessing electron-releasing groups on both aromatic rings in positions 3 and 5 of substituted 2-pyrazolines considerably enhanced the antidepressant activity. Chimenti et al. demonstrated that either the N1 acetyl group or N1-propanoyl substitution in position 1 increased the potency and selectivity towards the MAO-A inhibition. Considering that 2-pyrazolines are promising class of antidepressants and in the light of aforementioned findings, we aimed to obtain some N1 substituted acetyl 2-pyrazoline derivatives with 3,5-unsubstituted/substituted phenyl 2-pyrazoline as the common scaffold, with anticipated MAO inhibitory and antidepressant activities. All the compounds inhibited hMAO-A selectively and potently. Their inhibition was found as competitive and reversible. The compounds showed quite high MAO-A inhibition were selected for evaluating of acute and chronic antidepressant activities by Porsolt Forced Swim Test in mice. The results displayed that antidepressant activity of these compounds show similar rates with that of moclobemide in chronic application.

Birsen Tozkoparan has completed her PhD from Hacettepe University, Faculty of Pharmacy, and Department of Pharmaceutical Chemistry. She had completed her Post-doctoral studies from Westfäelische Wilhelms University, Institute of Pharmaceutical Chemistry, Münster, Germany and North-eastern University, Department of Pharmaceutical Sciences, Boston, USA. She is a Member of Hacettepe University. She has published more than 40 papers, mostly about analgesic/anti-inflammatory and anticancer drug research areas, in prestigious journals. She is Deputy Director of Hacettepe University, Institute of Health Sciences.

Cancer is recently announced as the leading cause of death worldwide. In the next two decades, the number of new cases is expected to rise dramatically. Chemotherapy is employed as a crucial part of the multimodal treatment of cancer. Unfortunately, the lack of selective and efficient agents constitutes a barrier against chemotherapy. Therefore research on the novel chemotherapeutics is receiving continuous interest. Widely-used Non-Steroidal Anti-Inflammatory Drugs’ (NSAIDs’) cancer chemo-preventive effects are demonstrated. Besides this, there are diverse studies asserting anticancer activities of 1,2,4-triazoles and their condensed derivatives. These conclusions inspired us to design novel 1,2,4-triazole-based condensed derivatives incorporating with NSAIDs’ structural motifs, namely 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles, which have been expected to have cytotoxic properties. The mentioned compounds were achieved by the reaction of an aminomercaptotriazole (1) derived from flurbiprofen with appropriate benzoic acids (a-j) in phosphorus oxychloride. Their initial cytotoxicity screening was assayed by NCI-Sulforhodamine B (SRB) test against human liver, breast and colon carcinoma cell lines. Compound 1h was further studied against enlarged hepatocellular carcinoma cell lines. Then, real-time cytotoxic effect of 1h was measured via RT-CES. For corroborating cellular response which 1h caused, cells were observed after staining with immune-fluorescent Hoechst dye. Furthermore, the effect of 1h was analyzed by measuring DNA content of the cell cycle phases with FACS method by using Propidium Iodide. Data showed that there was slight increase in Sub-G1 phase. These observations were helpful to enlighten possible mechanism of action of compound 1h triggered, and encouraged us for further studies.

Monique Hoon has completed her Msc in Pharmaceutical Chemistry and is pursuing her PhD at the North-West University, School of Pharmacy. She has a personal drive in helping to find a cure not only for Parkinson’s disease but also other neurodegenerative disorders. She has also demonstrated a sincere interest in Medicinal Chemistry, in particular the rational design of drugs and determination of physicochemical properties of new drug candidates.

Parkinson’s disease (PD) is a progressive, neurodegenerative disorder that affects approximately 1% of the population above the age of 60. The dopaminergic neurons which degenerate in PD are specifically those of the nigrostriatal pathway. Since this neuronal pathway delivers dopamine to the striatum, its loss results in a functional deficit of dopamine in the striatum. L-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the symptomatic relief of the advanced stages of PD. The oral bioavailability of L-Dopa is estimated to be about 10% and less than 1% of the administered oral dose reaches the brain unchanged. In an attempt to overcome the problems with peripheral L-Dopa metabolism, delivery difficulties and insufficient conversion of L-Dopa to dopamine in the brain tissue, an L-Dopa prodrug is envisioned in which L-Dopa is linked to the MAO-B inhibitor, lazabemide.

Ghada Refaat Ahmed Abdellatif is a lecturer in the Department of Microbiology and Immunology, Faculty of Pharmacy, MSA University. She received her Bachelors’ degree in Pharmaceutical Sciences from the Alexandria University. She received her PhD degree from Cairo University. Her research areas of interest are Immunology and Molecular biology.

Current methods available for detection of tuberculosis are insufficient for accurate diagnosis, at the same time the recommended molecular diagnostic methods have not been adopted in countries with limited resources. Glutamine Synthetase (GS) enzyme which is found in large amounts in culture filtrates of Mycobacterium tuberculosis was purified and used to develop an ELISA-based assay. The assay was used for the detection of GS in sputum of infected patients. The assay did not show any cross reactivity with microorganisms that are expected to be present in sputum specimen except for Pseudomonas aeruginosa. Eighty four sputum samples were subjected to ELISA and results were compared to acid fast stain and culture. Only 25% of the samples showed positive culture of which, 17.8% were typical M. tuberculosis and 7.1% grew Non-Tuberculous Mycobacteria (NTM). The assay detected 31 (97%) out of 32 clinically diagnosed TB and acid fast smear positive cases. Two additional cases were detected by ELISA among the group of patients with clinical TB and acid fast smear negative, while negative results were shown for the group of patients receiving antitubercular treatment and with NTM. Sensitivity and specificity of the assay compared to culture was 100% and 74%, respectively.

Objectives: To assess the effect of omega 3 fatty acids on cardiac necrosis biomarkers CK-MB and Troponin-I in Chronic Kidney Disease (CKD) patients undergoing elective Percutaneous Coronary Intervention (PCI). Background: Coronary artery diseases are the leading cause of mortality in CKD patients. In recent studies, it is shown that elevation in cardiac necrosis biomarkers, creatine kinase-MB (CK-MB) and troponin-I, have direct relation with increased cardiovascular risks following PCI in CKD patients. Methods: In this study, 50 CKD patients undergoing elective PCI were randomly assigned into two groups. First group received a loading dose (3 gr) of omega 3, 12 hours prior to intervention plus the standard PCI regimen (aspirin 80 mg and clopidogrel 600 mg loading then 75 mg/day). Second group received only the standard PCI regimen. The CK-MB and troponin-I levels were measured at baseline and 24 h after PCI. Results: A significant decreasing trend in CK-MB level (p=0.0021) and troponin-I level (p=0.004) was seen in omega 3 group versus control group after PCI. Conclusion: A 3 gr loading dose of omega 3 before PCI significantly reduces CK-MB and troponin-I after PCI in CKD patients.

Maryam Forouzmehr is student at the Shiraz University of Medical Sciences, School of Pharmacy. She is working on her thesis and will graduate this year with PharmD degree.

Objectives: Because of their ability to damage biological molecules, free radicals may affect several biological processes and lead to many diseases. Ginger (Zingiber officinalis) and peel of pomegranate (Punica granatum) used by human for thousands of years as therapy, are both medicinal plants that has many biological properties that are attributed to their wealth in phenolic compounds. Material & Methods: The influence of extraction methods on the content of these substances (method, temperature and extraction time) and consequently on their antioxidant properties were investigated. Three aqueous extraction methods were used: infusion, decoction and maceration. Results: The results indicated that maceration is the best extraction method of polyphenols (113.54 mg EGA/g of extract, 532.22 mg EGA/g of extract for ginger and pomegranate peel, respectively). The mixture of the two plants gave the highest phenolic content (888.52 mg EGA/ g of extract) and showed a great antioxidant activity (68.12%). According to these results, we conclude that this traditional therapeutic drink consisting of ginger and pomegranate peel has significant antioxidant activity using maceration as extraction method (p<0.05).

Ayla Kaya has completed his PhD from Anadolu University. She is a Professor and works at Department of Pharmaceutical Botany, Faculty of Pharmacy of Anadolu University and Head of Department. She has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of repute.

A group of Lamiaceae that has caused confusion over its generic boundaries are those species belonging to the complex surrounding the genera Satureja, Calamintha, Micromeria, Clinopodium and Acinos. In the current study, morphology characteristics of two endemic subspecies of Clinopodium troodi (Post) Govaerts, subsp. grandiflorum (Hartvig & Ã….Strid) Govaerts and subsp. vardaranum (Leblebici) Govaerts, previously treated as Acinos in Flora of Turkey, is studied for the first time and detailed descriptions and illustrations of general appearance of plants and their, leaf, bract, flower, calyx, corolla and fruit shapes are described and illustrated.

Emel Sönmez has graduated from Department of Biology, Anadolu University. She has studied one Master degree in Biology. Now she is pursuing other Master degree in Pharmaceutical Botany at Faculty of Pharmacy, Anadolu University.

Ajuga species are used to treat dysentery, malaria, high blood pressure, diabetes and many other diseases in the traditional medicine. In this study, two relict endemic Ajuga (Lamiaceae) taxa were investigated morphologically and anatomically. These relict endemic species exists the results of glacial and interglacial periods. Ajuga postii was collected from İçel: Çamlıyayla, and Ajuga relicta was collected from Kahramanmaraş: Çimen Mountain. Morphological investigations of Ajuga postii and Ajuga relicta were determined from fresh materials. Anatomical investigations were taken from cross-sections of root, stem and leaf. These two species do not have glandular or eglandular hairs on the stems. Anatomical features are generally similar. On the cross-section of the leaf of Ajuga relicta are seen eglandular hairs, but on the Ajuga postii are not.

U Gokcen completed her Master’s degree at Anadolu University, Department of Biology. Now, she is studying her second Master’s degree at Anadolu University, Faculty of Pharmacy and will continue her PhD studies at Osmangazi University, Department of Biology.

Achillea millefolium L. (Yarrow) has been used for therapeutical properties since ancient times. Also today, this plant is used in traditional and normal medicine. Commonly used parts of Achillea millefolium are herb (Herba Millefolii) and flowers (Flos Millefolii). Yarrow is used for healing the wounds, cramps, diuretic, karminatif, menstrual disorders, and as snack in Turkey. In this study, some Achillea samples which are sold as yarrow in the herbalists in Turkey are investigated. For this purpose, samples were identified, morphological properties were determined and the results were compared with European Pharmacopoeia for Achillea millefolium. The results of this study, 72 Achillea samples which were collected from different parts of Turkey and different herbalists, have been determined that Achillea biebersteinii, Achillea falcata, Achillea phyrgia, Achillea kotschyi and Achillea wilhemsii are sold as Achillea millefolium.

Salwa Elmeligie has completed her PhD from Cairo University and Postdoctoral studies from Faculty of Pharmacy, Iowa University, USA. She is Head of Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University. She is also Reviewer for Higher Education Institutions (HEIs), conducted by the National Authority of Quality Assurance and Accreditation of Education (NAQAAE), and credited trainer in Egypt. She has published more than 36 papers in reputed journals and has been serving as an Editorial Board Member of repute in addition to attending more than 20 training courses in Quality Assurance systems.

Special interest in targeted cytotoxic agents is directed towards protein kinases which play several roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy towards controlling different malignancies. In an attempt to develop novel antitumor agents acting through inhibiting Vascular Endothelial Growth Factor Receptor (VEGFR), a series of new arylphthalazine derivatives has been designed and synthesized. The targeted compounds were planned and implemented into docking studies to qualitatively predict their affinity and binding modes with VEGFR-2 kinase enzyme. Docking studies were performed on the designed compounds using Accelry’s Discovery Studio 2.5 software CDOCKER protocol. The structures of the synthesized compounds were confirmed by elemental analyses and spectral data (IR, 1H NMR, 13C NMR and Mass spectroscopy). Furthermore, biological screening in the National Cancer Institute (NCI), USA is applied to test the cytotoxic activity for the prepared compounds against full NCI 60 cell panel at a single dose (10 μM). Additionally, the target compounds are evaluated for their enzymatic inhibition of VEGFR-2 kinase.

Introduction: Gum arabic is a complex, loose aggregate of sugars and hemicelluloses composed of arabic acid nucleus connected with calcium, magnesium, potassium and sugars arabinose, galactose, and rhamnose. It is found in mechanically ground or spray dried forms. The solubility varies between 2 hours in the raw gum form and 20 minutes in spray dried form. This study tended to enhance the solubility by producing an instant soluble granulated form. Methodology: The study was performed using atomized fluid bed drier. 50 kg of raw gum, subjected first to mechanical comminuting into powder, then treated with water by spraying at rate of 200 ml/min for 90 minutes. The inlet temperature was 70oC, and the outlet temperature was 40oC. The cabinet temperature was 40oC. Finally, after water treatment process, the powder resized through mesh size of 40 micrometer and the microbial test was done for the finished product. Results: The solubility of the granulated instant soluble gum in room temperature was found to be less than 2 minutes compared to the spray dried form which is 20 to 30 minutes and 2 hours for mechanical ground gum. The volume increased to three times compared to the mechanical form. Conclusions: Granulation of gum under water spray significantly enhances the solubility and hence it is beneficial for uses in pharmaceutical technology as a binder, suspending agent, surface active agent and tablet coating materials.

Doaa A Zaky has obtained her Bachelor’s degree in Pharmaceutical Sciences from Cairo University, 2010. She is currently working as a Demonstrator in the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University.

Intestinal barrier dysfunction is frequently implicated in the etiology of septic complications following obstructive jaundice. The present study was conducted to investigate the potential gut barrier modulating effect of Vildagliptin (VLD), a Dipeptidyl Peptidase-IV (DPP-IV) inhibitor, on Common Bile Duct Ligation (CBDL) in rats. VLD (10 mg/kg/d; p.o.) was administered for 10 successive days after CBDL induction in male Sprague-Dawley rats. VLD reduced portal endotoxaemia induced by CBDL and improved body weight loss, colon and spleen indices. Moreover, VLD treatment reversed villous blunting, low villous density, mucosal thinning and inflammatory cell infiltration noticed in the ileal segments examined microscopically. These events were accompanied by the reduction in intestinal myeloperoxidase activity and lipid peroxidation, as well as the elevation of the major antioxidant molecule, glutathione. Furthermore, ileal DPP-IV was inhibited in association with the rise in ileal GLP-1 and ileal IGF-1 levels in the VLD treated animals. The current findings suggest that VLD antioxidant, anti-inflammatory, preservation of GLP-1 and enhanced production of IGF-1 account for the development of a hardwearing intestinal barrier that functions competently in absence of the supporting bile elements.

Aida Sefidani Forough has received her PharmD degree from Shahid Beheshti University of Medical Sciences which is ranked as the second best medical university in Iran. Currently, she is the Chief Manager at a hospital pharmacy after a 3-year experience of community pharmacy work. She serves not only as a part of the medical team but also is engaged in tasks such as drug utilization evaluation program, antibiotic resistance program and also is a member of the hospital’s drugs and therapeutics committee. She has one published paper and one under review.

Adverse drug events are mostly dose dependent and preventable. About 50% of these adverse effects are due to inappropriate dosing especially in patients with renal failure. We aimed to determine the impact of short message alerting on physicians’ drug dosing of patients with decreased renal function. Eighteen physicians accepted to enroll in the study. Their patients who received at least one of the six selected drugs were selected for evaluation. The patients with an estimated glomerular filtration rate of 50 ml/ minute or lower were randomly divided into two groups of case and control. An alert was sent to the physician in charge of the intervention (case) group. Physicians’ reactions was recorded as “dose adjustment”, “discontinuation of medication” or “none” and were compared in both groups. The reaction time of physicians before and after receiving alerts was recorded as well. 137 patients entered the study. The study results showed a significant difference in overall changes between the two groups (*** P<0.001). The rate of dose adjustment increased significantly after sending alerts to physicians (*** P<0.001). However, there was not a significant difference regarding discontinuation of medication between groups (P=0.76). On the other hand, prompt reaction of physicians (0-6 hours after sending short message) significantly increased after intervention (* P<0.05). Nevertheless, physicians’ reaction time in 6-24 hours and 24-48 hours was not changed significantly after intervention. The results of this study show that informing physicians about the renal function of the patients leads to appropriate dosing.

Anupam G Banerjee is currently pursuing PhD in Pharmaceutical Chemistry at the Department Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi (India). His research involves the Computer Aided Drug Design based synthesis of novel heterocyclic motifs as potential anti-inflammmatory and analgesic agents. His primary research interest lies in the development of NCE’s (New Chemical Entities) possessing anti-inflammatory potential. Apart from this, he also pursues his research interest in neuropharmacology by exploring new strategies for the synthesis of NCE’s as anti-convulsants. He has published 10 research papers in various journals of international repute.

A group of 5-substituted 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole tethered to a 5,6-diphenyl-1,2,4-triazin-3(2H)-ones were synthesized following a “hybrid-pharmacophore” approach and evaluated for anti-inflammatory and analgesic activity. The structure of the novel compounds were supported by FT-IR, 1H-NMR, 13C-NMR and elemental analysis. The derivatives (3a-3e, 4a- 4e and 5a-5e) were initially screened for in vitro anti-inflammatory potential by albumin denaturation assay. Compounds exhibiting comparable activity to standard drugs indomethacin and celecoxib were further assessed in vivo for anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. Of the fifteen synthesized derivatives, six compounds namely 3c, 3d, 3e, 4c, 4d and 4e exhibited superior anti-inflammatory activity in the acute, sub-chronic and chronic models of inflammation along with significant analgesic activity together with negligible ulcerogenic potential. These derivatives also exhibited reduced Malondialdehyde (MDA) content suggesting their protective effects to the inhibition of lipid peroxidation in the gastric mucosa. Derivatives 3c, 3d, 3e, 4c, 4d and 4e were found to be potent competitive COX-2 inhibitors with IC50 range of 2.28-3.17 μM. The binding modes of these active compounds into the COX-2 binding site through docking studies exemplified their consensual interaction and subsequent inhibition of enzyme thus corroborating the outcomes of in vitro and in vivo biological evaluation. Outcome of the following study involving “hybrids” embedded with two biologically active scaffolds may be further utilized for designing novel derivatives with potential anti-inflammatory and analgesic properties with superior safety profile than the current available therapeutic medication.

Nagendra Kumar is pusuing his PhD from Indian Institute of Technology (Banaras Hindu University), Varanasi (India). He is working in the field of nanoparticulate drug delivery system under the supervision of Professor B Mishra. He has qualified in IITJEE-2004, GATE-2008 and NET-2011. He has presented several poster/oral presentation in different national/international conferences/symposium/seminar. He is a Gold Medalist and IDMA Awardee for securing highest marks in the BHU in BPharm examinations. He has published several research articles in reputed journals.

Atorvastatin calcium (ATR) is a second generation statin drug prescribed for the maintenance of hyperlipidemia, atherosclerosis and cardiovascular complications. Despite of being blockbuster drug, its oral bioavailability is quite low (12%) and shows muscular toxicity. ATR loaded Poly (lactide-co-glycolic acid) nanoparticles (APLNs) has been successfully prepared to improve efficacy and safety profile of drug. Optimised batch of APLNs was subjected to pharmacokinetic, pharmacodyanamic and safety profile evaluation in Charles Foster rats. Pharmacokinetic study results with APLNs exhibited a significant enhancement of bioavailability, plasma halflife and mean residence time of ATR than commercially available tablet (Astin). Plasma lipid profile (triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and very low density lipoprotein) of APLNs and Astin treated hyperlipidemic rats were compared to elucidate the efficacy of APLNs over Astin. The dose of ATR in APLNs group was one half than that of Astin group. Efficacy of APLNs, however, was found equivalent to that of Astin group. Plasma safety profile (creatinine, blood urea nitrogen, creatinine kinase, lactate dehydrogenase and aspartate amino transferase) of APLNs and Astin treated group were estimated. APLNs exhibited equal efficacy and better safety profile at 50% reduced dose of ATR as compared to Astin.

Pavan Srivastava has completed his MPharm from Nirma University and is purusing PhD under the supervision of Professor S K Shrivastava from Indian Institute of Technology (Banaras Hindu University) Varanasi, India. He had also worked in the R&D centre of Piramal Healthcare at Ahmedabad for 1.2 years as a Research Associate. His current research interests are Medicinal Chemistry for the development of novel compounds to treat the neurogenrative disorders and anti-inflammatory agents.

A need for better anti-inflammatory agents with lesser side effects especially less ulcer forming capability is prevalent. The imidazo[1,2-a]pyridine derivatives possesses 5-LOX inhibition potential. A bio-isosteric replacement gave bicyclic nucleus- Indolizine and its derivatization resulted in compounds which showed anti-inflammatory activity. These derivatives were synthesised using 1,3-dipolar cycloaddition of heterocyclic N-ylides with electron deficient alkenes. The chemical structure of derivatives were confirmed by means of IR, 1H-NMR and elemental analysis. Five compounds (IND004, IND005, IND006, IND007 and IND008) showed significant inhibition of edema in carrageenan and arachidonic acid induced paw edema model at a dose equimolar to diclophenac sodium. Ulcerogenic study results revealed less ulcerogenic liability of IND004 compared to standard diclophenac sodium in rats. The in silico docking simulation confirmed their consensual interaction with the key binding site residues His-550, Phe-610 and Glu-614 of 5-LOX corroborating the outcomes of in vivo evaluation studies. These indolizine analogs were promising for the use as anti-inflammatory agents for acute inflammatory disorders especially with low toxic effects.

Nadia Tagnaouti has completed her PhD in Neuroscience at the age of 27 in Hamburg University, Germany. She has joined DiscoveRx, an innovative Drug Discovery provider, in 2008 and focused her activities in building the European Business as well as extending the company’s activities in Eastern Europe and the Middle East. While initial activities were mainly dealing with small molecules drug discovery, she has played an active role in broadening the usage of DiscoveRx Bioassays to Biologics and Biosimilars.

One of the major bottlenecks in the development of biosimilars is the need for good bioassays to create potency, stability and neutralizing antibody (NAb) assays. Ideal bioassays need to reflect the clinical mechanism of action (MOA) of the biopharmaceutical drug and should be simple, precise, reproducible and robust. Here, we discuss the development and application of diverse PathHunter® cell-based assays that cover distinct cellular mechanisms either downstream of or at the level of receptor engagement by biosimilar molecules. Importantly many of these assays rely on expression of native receptors thereby reflecting the clinical MOA of the biopharmaceutical drug. These assays are highly specific, quantitative, scalable, robust and utilize a homogenous mix-and-read protocol, which facilitates rapid and reproducible detection of drug potency. The technology is also amenable to accurate and sensitive detection of neutralizing antibodies, even in high concentrations of human serum through a simple chemiluminescent output. The assays are developed in a convenient ready-to-use format that minimizes assay variability often occurring due to cell culture. The cell preparation, bioassay protocol and reagents have been optimized to provide superior bioassay performance with high reproducibility (<10% RSD).

Nadia Tagnaouti has completed her PhD in Neuroscience at the age of 27 in Hamburg University, Germany. She has joined DiscoveRx, an innovative Drug Discovery provider, in 2008 and focused her activities in building the European Business as well as extending the company’s activities in Eastern Europe and the Middle East. While initial activities were mainly dealing with small molecules drug discovery, she has played an active role in broadening the usage of DiscoveRx Bioassays to Biologics and Biosimilars.

One of the major bottlenecks in the development of biosimilars is the need for good bioassays to create potency, stability and neutralizing antibody (NAb) assays. Ideal bioassays need to reflect the clinical mechanism of action (MOA) of the biopharmaceutical drug and should be simple, precise, reproducible and robust. To further enable NAb assays, there is an added need for serum/matrix tolerance and sensitivity. Here, we discuss the development and application of diverse PathHunter® cell-based assays that cover distinct cellular mechanisms either downstream of or at the level of receptor engagement by large molecules. Importantly many of these assays rely on expression of native receptors thereby refl ecting the clinical MOA of the biopharmaceutical drug. These assays are highly specific, quantitative, scalable, robust and utilize a homogenous mix-and-read protocol, which facilitates rapid and reproducible detection of drug potency. The technology is also amenable to accurate and sensitive detection of neutralizing antibodies, even in high concentrations of human serum through a simple chemiluminescent output. The assays are developed in a convenient ready-to-use format that minimizes assay variability often occurring due to cell culture. The cell preparation, bioassay protocol and reagents have been optimized to provide superior bioassay performance with high reproducibility (<7% RSD).

Maryam Abbasi is PhD candidate at Department of Medicinal Chemistry in Isfahan University of Medical Sciences. Her thesis is about prediction of new Hsp90 inhibitors by pharmacophore modeling and virtual screening, synthesis and biological test of predicted ligands.

In the present study, 3, 4-isoxazolediamide derivatives were proposed as Hsp90 inhibitors for anti-cancer therapy. Genetic algorithm of partial least square (GA-PLS) methods as ligand-based methods was performed to build models to predict the inhibitory activity of Hsp90. The validation of models was performed by leave-one out (LOO) cross-validation method and Y-randomization test to check their predictability. The created GA-PLS model indicated the importance of size, shape, symmetry, and branching in a molecule in inhibitory activities of Hsp90. Applicability domain of the models was determined to screen new compounds. Also, molecular docking studies as a structure-based method were conducted to study the mode of interaction of 3, 4-isoxazolediamide derivatives with Hsp90. The Hsp90 binding site was verified according to the previous studies. The two main residues at the bottom of pocket were Asp93 and Thr184. The docking study indicated that two hydroxyl groups in the resorcinol ring were very important in interacting with Asp93 and the orientation of these groups was related to substitution of different R1 groups.

Rabab Mohammed has completed her PhD from the University of Mississippi, USA. She is the Chairman of the Department of Pharmacognosy, Beni Suef University, Egypt. She has published more than 25 papers in reputed journals and has been member of the committee of 15 PhD and Master’s students in the field Of Natural Product Research.

Ten compounds, including five sterols (1-5), three sesquiterpenes (6-8) and two fatty acid esters (9-10) have been isolated from the Red Sea soft coral Sinularia terspilli. The anti-leukemic, antileishmanial, antimicrobial, and antimalarial activities, of the isolated compounds and some acetylated derivatives (1Ac, 3Ac, 4Ac, 5Ac) were evaluated. Compounds 4, 5, and 5-Ac exhibited strong cytotoxic activity against human leukemia cell lines HL60 and K562 with IC50 values of 4.0, 2.0, and 25 nM respectively for HL60 and 5.0, 3.0, and 40 nM for K562.