12^th World Pharma Congress October 16-18, 2017 Budapest, Hungary

Jee H Jung has his expertise in isolation, structure elucidation, and biological evaluation of new compounds from marine organisms. In recent years, his research was focused on the study of bioactive compounds from marine invertebrate-derived microorganisms. Further studies on optimization of lead compounds by docking simulation-based analogue synthesis and enhancement of bioavailability by nanoparticle formulation are also his major research interests.

Previously, we isolated a new compound paecilocin A as a PPAR-γ binding molecule from the jellyfish-derived fungus Paecilomyces variotii. Based on the molecular framework of paecilocin A, a series of phthalimide analogues were synthesized and evaluated for PPAR-γ binding activity. In a subsequent screening for competitive binding activity, 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) showed good PPAR-γ agonistic activity. Since one of the functions of PPAR-γ is suppression of inflammatory responses, the present study aimed to investigate anti-inflammatory activity of PD1. Transcriptions of mRNA were determined by reverse transcriptase-PCR. Inflammatory protein expressions were determined by ELISA and Western blot method. In Lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells, PD1 suppressed the induction of pro-inflammatory factors including inducible Nitric Oxide Synthase (iNOS), Nitric Oxide (NO), Cyclooxygenase 2 (COX-2), Tumor Necrosis Factor α (TNF-α), interleukine 1β

(IL-1β), and interleukine 6 (IL-6) in both mRNA level and protein level. In parallel, PD1 enhanced expression of anti-inflammatory factors such as arginase-1 and interleukine 10 (IL-10). PD1 simultaneously suppressed LPS-evoked Nuclear Factor kappa B (NF-κB) p65 subunit phosphorylation in macrophages. The anti-inflammatory mechanism of PD1 is proposed to be via inhibition of NF-κB pathway. In subsequent in vivo animal experiment employing carrageenan-induced acute inflammatory paw edema model, PD1 showed significant reduction in paw swelling. Histological analysis of tissue sections revealed reduction of cellular infiltration of immune cells in PD1-treated groups. These findings suggest that PD1 may serve as an anti-inflammatory lead.

Seong Gu Hwang has completed his higher qualification from Hankyong National University, Korea and currently working in Department of Animal Life and Environmental Science, Hankyong National University, Korea.

Euphorbia tithymaloides L. is native plant growing in tropical and subtropical areas of Asian countries. It has been known as traditional medicine with a wide range of healing properties such as anti-oxidant, anti-inflammatory, anti-hemorrhage, antidiabetic, antibiotic, and anti-tumoral. It contains some bio-active compounds such as beta-sitosterol, cycloartenone, octacosanol, oxime, etc. In earlier in-vitro study, octacosanol has reduced the expression of mRNA or protein of pro-inflammatory cytokines. This study is aimed to evaluate the anti-inflammatory activity of Euphorbia tithymaloides L. ethanol extract (ETE) in RAW264.7 macrophages. Anti-inflammatory activity was studied by treating RAW264.7 murine macrophages cells with increasing concentration of the ETE extract (50, 100, 200, and 400 μg/ml). Lipopolysaccharide (LPS) was used to activate the cells. CCK-8 assay and Griess reagent were used to examine the cell viability and Nitric Oxide (NO) production, respectively. The result shows increasing concentration by 200 μg/ml increases cell proliferation then declines. On the other hand, Nitric Oxide (NO) production decreases with the increase of concentration of the extract. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) was used to measure the mRNA expression of pro-inflammatory cytokines. Western blotting was also done to examine the effect of ETE extract on the protein expression of RAW264.7 murine macrophages cells. It has been shown that increasing concentration decreased the mRNA expression of IL-6, iNOS, COX-2, TNF α, IFN γand NF-kB, as well as protein expression. In conclusion, the results support the empirical use of Euphorbia tithymaloides L. ethanol extract as an anti-inflammatory medicine.

Rizki Fitriani has completed her Master’s degree in Natural Products Chemistry from Bandung Institute of Technology. She is currently a Doctoral Candidate at the same university. Her research interests focus on natural products isolation and their structural characterization, as well as bioassay on the isolated pure compounds.

Morus is one genus of plants belonging to Moraceae family that has important economic and medicinal value. The leaves of some Morus plants are indispensable food for silkworm, while their root bark has been used for treatment of diabetes, arthritis, and rheumatism. Previous phytochemical investigation showed that this genus produces a variety of phenolic compounds

including stilbenes, 2-arylbenzofurans, flavonoids, and Diels-Alder adducts. Diels-Alder type adducts are the unique ones due to their complex and fascinating structures. Some of these compounds showed important and various bioactivities, such as cytotoxicity, antioxidant, antimicrobial, anti-inflammatory, and antiviral. The source of biologically important secondary metabolites was obtained conventionally from the intact plants. However, recent development in plant biotechnological approach has shown the possibility of plant tissue cultures as an alternative source for producing bioactive secondary metabolites. Therefore, the isolation and characterization of secondary metabolites from Morus alba var. shalun root cultures were implemented in this research. Three new Diels-Alder type adducts (1-3) together with two known Diels-Alder type adducts (4-5) were isolated from the EtOAc extract of liquid medium and MeOH extract of Morus alba var. shalun root cultures. The structures of the isolated compounds were elucidated based on a comprehensive analysis of spectroscopic data, including 1D, 2D, and MS data. Compound 1-5 exhibited significant cytotoxicity against murine leukemia P-388 cells with IC50 values 0.7, 0.7, 2.0, 1.7, and 0.6 μg/mL respectively. These results demonstrate the potency of compound 1-5 as the lead compounds for anticancer agent.

Wen Tan is a Professor and Dean at Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China. He has his

expertise in “Thousand Talents” plan in China (2012). Professor Tan earned his medical degree at HB Medical School in China and earned his PhD. from University of Nebraska Medical Center in USA. After post-doc trainings at Harvard Medical School, he joined Howard Hughes Institute& Columbia University in USA as an associate research scientist and research assistant professor. In late of the nineties, he returned to China as a founder of a pharmaceutical research company which has successfully registered more than ten generic & innovative drugs for China market since.

Cardiac ischemia or hypertrophy involves multiple mechanisms and may lead to heart failure. Few medicines are now available for effective treatment. STVNa, derived from Stevia, has been shown beneficial effects in protection of acute cardiac ischemia. Our recent studies demonstrated that in animals with chronically coronary occlusion, consecutive oral treatment of STVNa significantly ameliorated the deterioration of cardiac function with reduced area of infarction and apoptosis. Long-term treatment of STVNa in Transverse Aortic Constriction (TAC) rats also protected the heart from fibrosis and hypertrophy remodeling and improved both cardiac systolic and diastolic function. In isoproterenol treated ventricular myocytes, STVNa reduced hypertrophy, inhibited the increases in cytosol calcium or ROS, and preserved contractility and mitochondrial membrane potential. Proteomic analysis, cell biochemistry and electrophysiological studies indicated that STVNa protected the heart against fibrosis and remodeling of metabolite and electrophysiology during ischemia and/or reperfusion injury or hypertrophy.

Dnyanesh Limaye is currently working as a Faculty III at Hochschule Hannover Germany. He is a fellow of Information and Design from University of Applied Sciences and Arts, Hannover, Germany. He has his expertise in Self-medication practices among university students from Karachi, Pakistan.

Introduction: Self-medication, practiced globally is an important public health problem. Research studies have indicated inappropriate self-medication results in adverse drug reactions, disease masking, antibiotic resistance and wastage of healthcare resources.

Objectives: The objective of the study is to explore overall self-medication and antibiotic self-medication prevalence among students of university students in Karachi, Pakistan along with probable reasons, indications, and sources of advice for self-medication.

Methods: A descriptive, cross-sectional, questionnaire-based study was carried out among students from University of Karachi, Pakistan during the time period of September to November 2016. Pretested questionnaire was distributed to 320 students and the collected data was analyzed using IBM SPSS version 24.

Results: From 320 students, 311 (83 male and 228 female) students participated in the study giving a response rate of 97%. Prevalence of self-medication was 66%. Belonging to higher monthly family income group was associated with likelihood of self-medication. Antibiotic self-medication prevalence was 39%. Lack of time (39%), and old prescription (35%) were the main reasons for selfmedication. Pharmacy shop (75%) was the main source for self-medication. In case of antibiotics, 44% students changed the dosage of antibiotic and 50% students stopped antibiotics after the disappearance of the symptoms.

Conclusion: Antibiotic self-medication (39%) and self-medication with other drugs among university students of Karachi is a worrisome problem. Our findings highlight the need for planning interventions to promote the judicious use of general medicines as well as that of antibiotics.

Thanasan Nilsu is doing his PhD in Applied Biological Sciences at Chulabhorn Graduate Institute, Chulabhorn Royal Academy of Science, Bangkok, Thailand. He has been working on the isolation of Lycopodium alkaloids from Thai club mosses and derivatization of huperzine A. His research also includes pharmacological evaluation of natural and synthetic compounds in mammalian cell culture.

Statement of the Problem: Lycopodium alkaloids are quinolizine, pyridine and pyridone alkaloids isolated from club mosses (Lycopodiaceae). The most notable alkaloid from this group is huperzine A, which is a potent reversible Acetylcholinesterase (AChE) inhibitor. Studies on Lycopodium alkaloids from club mosses in Southeast Asia are deficient. This work aimed to phytochemically investigate club mosses native to Thailand and the Philippines.

Methodology: Whole plants of H. squarrosa collected from Thailand and the Philippines were extracted with methanol. The methanolic extracts were subjected to acid-base extraction. The obtained alkaloidal fractions were further purified through column chromatography.

Findings: H. squarrosa from Thailand yielded four alkaloids. Two known Lycopodium alkaloids were identified to be huperzine A (1) and 12-epilycodoline N-oxide (4). Squarrosine A (2) was a new fawcettimine-type Lycopodium alkaloid which possessed intramolecular hydrogen bonding. (R)-2-piperidineacetic acid (5) has never been reportedly isolated. This alkaloid was speculated to derive from precursors of Lycopodium alkaloids. From Philippine H. squarrosa, huperzine A (1) and pyrrolhuperzine A (3), a new lycodine-related Lycopodium alkaloid bearing a rare pyrrole moiety, were isolated. Semi-synthetic approaches to pyrrolhuperzine A (3) were achieved to confirm its structure elucidation, and two plausible biogenetic pathways from huperzine A (1) to pyrrolhuperzine A (3) were proposed. Furthermore, huperzine A (1) was chemically transformed into three amide derivatives (6-8). The newly isolated and semi-synthetic alkaloids were assayed for their anti-AChE activities. Huperzine A derivatives 6 and 7 exhibited strong AChE

inhibition.

Conclusion & Significance: Thai and Philippine H. squarrosa contained high amount of Huperzine A (1) (0.014% and 0.13%, respectively). The synthesis of pyrrolyl derivative of Huperzine A has been accomplished for the first time.

Maria Pia Fuggetta is a professor of Pharmacology at Institute of Translational Pharmacology, Italy. She is expertise in a laboratory test based on determination of cytokine profiles: a promising assay to identify exposition to contact allergens and predict the clinical outcome in occupational allergic contact dermatitis.

Stilbene compounds are a family of phytoalexins, synthesized by different plants where they are induced by stress conditions such as infection, trauma and UV-irradiation. Among stilbenes, Resveratrol, (3,5,4´-trihydroxystilbene RES), and its glucoside Polydatin (3,5,4'-trihydroxystilbene 3-O-beta-D-glucopyranosid POLY), have increasingly gained scientific interest. POLY is structurally related to RES in which the oxidrilic residue is substituted by a glycoside group. This substitution induces changes in the biological properties. RES is susceptible to oxidative degradation while POLY, a precursor of RES is more resistant to enzymatic oxidation, POLY is highly soluble in water, enter the cells by active transport and is more readily absorbed by the intestine. RES and POLY, show many antitumor properties including apoptosis induction and inhibitory effects on cancer cell proliferation, angiogenesis, metastasis, and inflammation. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Melanoma is the most common cutaneous malignancy in Caucasian population whose frequency is increasing at an alarming rate. In previous studies, we have demonstrated that RES inhibits the proliferation of human melanoma, also resistant to Temozolomide, and we have suggested that the mechanism by which RES exerts its antitumor activity in melanoma cells correlates with apoptosis induction, reduction of telomerase activity and hTERT gene transcript levels. Objective of the present study is to investigate the antitumour activity of POLY in vitro and in vivo on a murine syngenic model of melanoma. We tested in vitro the antiproliferative effects of POLY on tumour growth and compared its effectiveness with the activity of RES on B16 melanoma cell line. In addition,

cell cycle progression, induction of apoptosis and telomerase inhibition were also investigated. We found that POLY, like RES, can inhibit cancer cell proliferation in B16 melanoma in a time- and concentration-dependent fashion, and that the POLY at lower concentrations resulted to be more effective than RES. In vivo experiments were performed in a syngenic murine model in which male C57BL/6J were injected with B16 melanoma cells with different treatment schedules to assess the chemopreventive and/or therapeutic activity of POLY. The results show a significant reduction of tumor mass, measured during POLY treatments and a significant survival increase in mice treated with POLY pre and post-tumor implantation. Though preliminary these results suggest that POLY, for its clinical potential, both in terms of disease prevention and treatment, could be considered a good candidate in melanoma management.

We confirmed that crocin prevented N-SMase activation, ceramide production and JNK phosphorylation. Exploration of the crocin’s preventive mechanism in oxidative stress-induced cell death revealed that the activities of GSH reductase. These results strongly support the importance of the proposed GSH-dependent inhibitory mechanism in oxidative stress-mediated cell death. The effects of saffron extract and crocin on improving ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks has been reported. Based on these results, it became evident that saffron extract and crocin prevent the inhibitory effect of ethanol on Long-Term Potentiation (LTP) in the denatate gyrus in vivo. We examined the sleep-promoting activity of crocin by monitoring the locomotor activity and electroencephalogram after administration of crocin to mice. Crocin (30 and 100 mg/kg) increased the total time of non-REM sleep by 60 and 170%, respectively, during a 4-h period from 20:00 to 24:00 after its intraperitoneal administration at a lights-off time on 20:00. Furthermore, the anti-cancer activities against colon cancer cell lines, skin and colon cancers in mice are also discussed.

Temitope Oyeneye completed her Graduation at Olabisi Onabanjo University and internship at Lagos University Teaching Hospital in Lagos, Nigeria. Presently, she is working as Pharmacist at Drug Consult Pharmacy, Nigeria. She has years of experience in interpreting a prescription and administration of pharmaceutical drugs in both government hospital and private corporate pharmacy stores.

The success or failure of any pharmacovigilance activity depends on the reporting of suspected adverse reactions. ADR reporting with yellow cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). ADR reporting among health care workers in Nigerian tertiary institutions is at a very low practice. A cross sectional study was made involving 75 medical doctors, 75 pharmacists and 30 nurses was surveyed with self-administered questionnaire which had undergone some modification to suit Nigerian environment. The questionnaire was validated through scrutiny in the Clinical Pharmacy department of University of Lagos and the zonal head of the NPC in LUTH. The Questionnaire was distributed through various heads of the units and professional acquaintances and was allowed to stay with them so as to allow attending to the question. The questionnaire sought the demographics of the HCPs; the factors they perceived may influence pharmacovigilance practice and suggestion on the possible way to improve ADR reporting. The result gave 95.6% response rate. A majority of the HCPs responds to positive impact in improving ADR reporting and factors militating the practice. Education and training was the most recognized means of improving ADR reporting. Adverse drug reaction reporting among the Nigerian health care professional proves to be inefficient and lack a proper data base documentation. Though, there has however been a slight improvement when compared to previous studies. Social workers and all sectors of the health care system need to be involved. Governments needs to include private hospitals, retails dispensaries and traditional medicine. PV reporting centre should also be at primary health centre, effort must be to train staffs who would flag off the monitoring and documentation of ADR, lack of local expertise in pharmacovigilance could be tackled through developing exchange programmes with NAFDAC and sharing of best practices, there should be established organizers of public health and drug access campaigns in local languages and with regional surveillance stem and creating a specific centre for pharmacovigilance in all hospitals will help the advancement.

Andras Kern completed his PhD in Genetics at Eotvos Lorand University, Hungary. He is currently working as Staff Scientist and studying the ghrelin receptor signaling in neuronal tissue at Scripps Research Institute (TSRI).

A major challenge in the field of G-Protein Coupled Receptor (GPCR) drug discovery in CNS is developing specific drugs without side effects. Selection of a drug candidate is traditionally based on canonical signal transduction pathways after expression of the individual GPCRs in heterologous cell lines. However, these assays do not predict the response of target cells in the native tissue; therefore, the desired clinical outcome is often not met. For example, drugs designed for dopamine (DA) receptor subtypes act on all neurons expressing this subtype, but selectivity requires knowledge of a specific target that discriminates between neuronal subtypes. In neurons, the targeted GPCR is frequently not present in isolation, but with other GPCRs. Some GPCRs are capable of forming heterodimers with a specific GPCR partner resulting in cell and tissue specific modification of canonical signal transduction. To achieve more selectivity for regulating DA signaling, our research focused on regulating DA signaling by target neurons that express dopamine receptor (D1R or D2R) and ghrelin receptor (GHSR1a) heterodimers. We exploit the novel concept that in GPCR heterodimers a neutral antagonist of one protomer can modify the function of the partner protomer by an allosteric mechanism. We detected that D2R:GHSR1a and D1R:GHSR1a heterodimers exist in neurons of native brain tissue resulting in allosteric modification of DA signaling. Our results show that dopamine receptor heterodimers in hypothalamus can regulate food intake in animals through D2R:GHSR1a. We found that in hippocampus D1R:GHSR1a heterodimers regulate DA-dependent memory performance. We show DA signaling through these heterodimers is modulated by a GHSR1a antagonist. Hence, treatment with a GHSR1a antagonist provides a selective way of blocking or enhancing DA signaling in neurons expressing the heterodimers without affecting signaling in neurons expressing D1R or D2R alone. These results show potential opportunities for developing more selective therapeutic agents for treating psychiatric disorders involving abnormal DA signaling.

Arpa Petchsomrit is a PhD student at Prince of Songkla University, Songkhla, Thailand. She has her expertise in development and evaluation of liquid and solid

dosage form of self-emulsifying drug delivery system for oral application.

Resveratrol is a polyphenol compound found in grapes and other food products. It exhibits numerous pharmacological activities including anti-oxidant and anti-carcinogenic properties. Therapeutic application of resveratrol is limited due to its low aqueous solubility. The purposes of this study were to develop self-emulsifying resveratrol sustained release alginate beads and assess anticancer

activity on gastric cancer cells. Floating alginate beads were prepared by ionotropic gelation method and used calcium carbonate as gas forming agent. Use of different concentrations of sodium alginate, self-emulsifying resveratrol, pore forming agent (Kollicoat® IR), and drying method showed different effects on physical properties and in vitro drug release in each bead formulation. All formulations floated immediately and remained floating over 72 h. The optimized formulation consisted of 2% w/v sodium alginate and 15% w/w self-emulsifying resveratrol. Freeze dried beads and oven dried beads showed sustained release profiles and values of cumulative release profiles in 8 h were 97.22% and 84.60%, respectively. Conversely, liquid self-emulsifying resveratrol gave immediate release approximately 80% in first hour and almost completely released (99.75%) in same period. Anticancer activity on AGS cells

of both floating self-emulsifying resveratrol beads and liquid self-emulsifying resveratrol (IC50 23.53±0.66 and 23.99±1.05 μg/ml, respectively) were equivalent to that of unformulated powders dissolved in DMSO (IC50 23.75±0.53 μg/ml). Consequently, alginate bead preparation process did not have any effects on pharmacological activity. This study disclosed that floating self-emulsifying beads could enhance the solubility, prolongs drug release, and may have potential for gastric cancer treatment.

Buket Aksu completed her Graduation from Istanbul University and Doctorate degree in Quality by Design (QbD) at Ege University. Currently, she continues her academic career at Istanbul Kemerburgaz University; also works as Consultant in Pharmaceutical Industry. She has given numerous speeches and training programs on QbD, Industrial Pharmacy, Management Skills, Registration and Patent, R&D and Innovative Sales.

Despite continuous innovations in the pharmaceutical industry for developing futuristic new drug products, there has been a repeated set back owing their low quality and manufacturing standards. The studies and tests required to deliver a new drug to patients last up to 15 years, and cost over 800 million $. Even after a drug is invented, its development may fail due to the proven impossibility of its safe manufacture in a large scale and incompliance with the relevant specifications. The length of the approval process and the requirement to start over for a development cycle of any changes due to the stalemates, even product is licensed has led to concerns for many decades. With the consequent growing concerns and criticism, in this regard, in 2002, the current Good Manufacturing Processes (cGMP) was introduced to improve and modernize the rules that regulate the drug manufacturing and quality. Subsequently, in 2005, the guideline Q8 of the International Conference on Harmonization (ICH), which focused on the content of the Module 3.2.P.2 of the Common Technical Document (CTD), was published. The ICH instituted a series of quality guidelines all emphasizing the adoption of systematic principles of Quality by Design (QbD) and Process Analytical Techniques (PAT). QbD is a patient-centric science and risk-based approach for developing drug products with better understanding of the products and processes by planning quality at first hand in order to avoid quality crisis and using the knowledge obtained during the life-cycle of the product to work on a constant improvement. Implementation of QbD-based strategies in pharmaceutical development would

provide excellence and significant time shortening in product development, and enormous flexibility in regulatory compliance. It has been emphasized before if the principles described in the ICH Q8, Q9 and Q10 guidelines are implemented together in a holistic manner, this provides an even greater assurance that the patient will receive product that meets the critical quality attributes.