Day 1 :
Keynote Forum
Solomon Habtemariam
University of Greenwich, UK
Keynote: New anti-inflammatory compounds from old medicines: The science and art of Pharmacognosy research in the 21st Century
Biography:
Solomon Habtemariam has completed his PhD, 2 years of Post-doctoral Research (Strathclyde Institute for Drug Research) and 4 years of Lectureship at Strathclyde University. Since then, he has been a leader of researches on bioassays & natural products-based drug development at the University of Greenwich and Founder/Owner of Herbal Analysis Services. He is an Elected Fellow of the Royal Society of Medicine, the Royal Society of Chemistry, the African Academic Institute and the African Academy of Sciences. He has published over 130 papers in peer reviewed journals and has been serving as an Editorial Board Member for many journals.
Abstract:
For thousands of years, mankind has used nature as a source of medicine. Despite the tremendous advances in medicinal chemistry and/or drug discovery areas over the years, our modern pharmacy even today employs a significant number of drugs that trace their origin back to natural products. Inflammatory diseases, especially chronic disorders such as arthritis, inflammatory bowel disease, psoriasis, sepsis, etc., continue to be a burden to large number of people and national health services throughout the world. With the severe limitations of the existing anti-inflammatory drugs (e.g. cost, side effects and efficacy) for such diseases, the appetite for novel drugs is as great as ever. During the past three decades, our researches have been mainly focusing on the identification of novel pharmacologically active compounds from medicinal plants. By using the bioassay-guided isolation approach, we have identified numerous compounds that showed potential in the various experimental models. In this communication, case examples are presented where the anti-inflammatory potential of crude and purified natural products have been validated through cell-free, cell-based and animal models of inflammation.
Keynote Forum
Anna Szemik-Hojniak
University of Wroclaw & University of Applied Sciences-Walbrzych, Poland
Keynote: A new series of heterocyclic N-oxides as promising drug candidates
Biography:
Anna Szemik-Hojniak has completed her PhD in Radiochemistry from the University of Wroclaw and Post-doctoral studies in Physical Chemistry and Radiochemistry from Solvay Foundation (Belgium), KU Leuven (Belgium) and Centre of Nuclear Researches (Strasburg, France). She occupies with Organic Molecular Photo physics, published more than 45 papers and serves as a reviewer in scientific journals. In the years 2002-2011, she served as the INWES Board Director (2002-2011) for INWES corporation- the operational partner of UNESCO. In 2007, at the University of Wroclaw, (Poland), she organized international workshop on “Strategies for the Highly Skilled Global Workforce”. In 2011, she was awarded with Distinguished Service Award. Presently, she is INWES-ERI General Secretary and the Board Director (Headquarters-Ottawa, Canada). In 2014 and 2015, she organized Mini Symposium “Photo physics of Electron and Proton Transfer” in the framework of ICCMSE- 2014 conference, in Athens (Greece) and presented the Keynote lecture on “Behaviour of styryl derivatives under the light irradiation” during 4th-Annual European Pharma Congress-2015 in Valencia (Spain).
Abstract:
Recognition of type of interactions and binding mechanism between receptor and an introduced bioactive agent (drug), requires the knowledge of several components. Of which primary importance are: lipophilic (hydrophobic) factor, electronic (substituent) parameter, steric factor, ability to form hydrogen bonds as well as charge transfer (CT) or proton transfer (PT) nature of the drug. Aromatic heterocyclic compounds, such as derivatives of pyridine N-oxides, due to their practical impact on pronounced biological activity, occupy in this field a very particular place. They exhibit antifungal, antiviral or antibiotic properties and many of their derivatives show herbicidal activity. Furthermore, they are also able to inhibit electron transport across cell membranes or mediate proton transfer across the mitochondrial membrane. N-oxides and many of their derivatives are characteristic of CT interactions resulting from a partial transfer of electron density from the HOMO orbital of the electron-rich functional group to the LUMO orbital of electron-poor substituent. Their electron donating or proton accepting abilities can be easily varied by appropriate substitution at certain position of the π-electron system. In this presentation, X-ray structures and spectral properties in the gas phase and solution of nitraminopyridine N-oxides containing the –NH-NO2 substituent in position 2 with respect to the –NO group and methyl group in different positions of the pyridine ring [3, 4, 5 or 6, e.g. 3-methyl-2-nitraminopyridine N-oxide (3M)] are demonstrated. In the solid state, two centrosymmetric crystals form a dimer where a mutually parallel or perpendicular location of the two monomers in the crystal lattice results in the corresponding molecular (H) or proton transferred (PT) form. In the (H) form, the amino hydrogen is at the –NH-NO2 group while in the PT form, it is located at the NO group. Between both molecules in dimer, the N-H...O or O-H...N intermolecular hydrogen bonds of different strength are formed. Interestingly, both forms exhibit favourable for drug-receptor CT interactions. Theoretical TD DFT calculations show that the S0→S1 electronic transition in these compounds is of the ππ* type in the (H) forms and a mixed ππ* + n, π* type in the PT forms. Additionally, contrary to the solid, the monomeric forms are present in the solution and prototropic equilibria of amino (H) <-> imino (PT) type should be taken into consideration.
Keynote Forum
Hussam AS Murad
King Abdulaziz University, Saudi Arabia
Keynote: Potential Benefits of Roflumilast in Bronchial Asthma
Biography:
Hussam AS Murad worked as a Professor at Pharmacology and Clinical Pharmacy Departments in a number of universities in Egypt and Saudi Arabia. He has an experience of about 25 years in teaching and research. Murad has worked in 10 research projects as a principal investigator and as a first co-investigator in another four. He has got funds from King Abdulaziz City for Science and Technology (KACST), Riyad, SA, and Deanship of Scientific Research, King Abdulaziz University (KAU), Jeddah, SA. He received the award of scientific publication from KAU, in 2015 and in 2017.
Abstract:
Statement of the Problem: Bronchial asthma affects about 150 million people all over the world. The inflammatory mediators released from eosinophils, T-helper 2 lymphocytes, airway epithelium, and airway smooth muscle contribute to chronic inflammation and remodeling. Airway remodeling leads to progressive decline of lung functions and it is steroid resistant, thus there is a need for new medications with better anti-remodeling effect. Phosphodiesterase (PDE)-4 inhibitors have anti-inflammatory and anti-remodeling properties. Roflumilast; a selective PDE-4 inhibitor; is approved as an add-on therapy for chronic obstructive pulmonary disease (COPD). The inflammation in COPD and severe asthma is neutrophilic while in asthma it is eosinophilic. Consequently, investigating effects of roflumilast in eosinophilic inflammation is beneficial. During exacerbation of murine acute asthma, roflumilast (oral and intratracheal) decreased airway macrophages, eosinophils, neutrophils, T-helper 2 cytokines, and hyperresponsiveness (AHR). In contrast, steroids failed to affect AHR or neutrophil numbers which are considered important parameters for exacerbations of human asthma. Addition of roflumilast to high-dose fluticasone in patients with uncontrolled asthma improved asthma possibly through affecting the neutrophilic component of the disease. Ability of roflumilast to reduce sputum eosinophils, neutrophils, and macrophages makes it of potential off-label use in asthma. In a lipopolysaccharide-induced inflammation model in Wistar rats, "inhaled" roflumilast N-oxide decreased neutrophils in the bronchoalveolar lavage fluid (BALF). Thus "inhaled" roflumilast N-oxide could be as a useful alternative to oral roflumilast in airway disorders. Conclusion & Significance: Roflumilast (oral or inhalational) significantly decreases airway hyperresponsiveness, the elevated inflammatory mediators, the elevated BALF levels of matrix metalloproteinase-9 and its inhibitor (TIMP-1), and remodeling in both human asthma and animal asthma models. These benefits are due to its anti-inflammatory and anti-fibrotic effects. Investigating the effects of a triple inhalation therapy consisting of roflumilast, corticosteroids, and long acting β2 agonists in chronic asthma models is a point for research.
- Pharmacological Sciences | Pharma Consulting & Services | Bio-Pharmaceutics | Bioinformatics Pharmaceutical Chemistry
Location: LEON
Chair
Solomon Habtemariam
University of Greenwich, UK
Co-Chair
Anna Szemik-Hojniak
University of Wroclaw & University of Applied Sciences-Walbrzych, Poland
Session Introduction
Maria A Miteva
University Paris Diderot, France
Title: Pharmacogenomics of cytochrome P450: Effects of missense mutations on drug metabolism
Biography:
Maria A Miteva has completed her PhD in 2000 at the Bulgarian Academy of Science. She has vast experience on bioinformatics, chemoinformatics, in silico drug design and pharmacology. She is a Research Director at Inserm Institute and a Leader of the team “Virtual screening, PPI & ADMET in silico” (MTi, Insem U973, Paris Diderot University). She has published over 80 scientific articles in peer-reviewed journals and she has edited a book “In silico Lead Discovery” (Bentham Sci). Currently, she is an appointed Member of the Editorial Board of 5 international journals in the field of Bioinformatics and Drug Design and Associated Editor for BMC Pharmacology Toxicology.
Abstract:
Pharmacogenomics investigates DNA and RNA variations in the human genome related to drug responses. Cytochrome P450 (CYP) is a supergene family of drug metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical significance because it metabolizes approximately 20% of clinically administrated drugs and represents several variant alleles leading to adverse drug reactions or altering drug efficacy. Recent progress on understanding the inter-individual variability of the CYP2C members and the functional and clinical impact on drug metabolism will be presented. The structural bases and molecular mechanisms of amino acid variants of CYP2C members that affect drug metabolism will be discussed.
Khalid Awad Al-Kubaisi
University of Gloucestershire, UK
Title: Identifying risk factors for incautious use of non-prescription drugs among university students in Emirates
Biography:
Al Kubaisi is a post-gradute researcher in his final year of PhD program in Public Health from Gloucestershire University, UK. He awarded his master degree, Excellent with First Honours, in Public Health (MPH) from Hamadan bin Mohamed Smart University, Dubai during the academic year 2010- 2012. He attended his under graduate school at the University of Baghdad where he received his Bachelor degree in Science of Pharmacy in 1996. He spent ten years working as a pharmacist in UAE. His research’s interest is in self-medication practice and in the use of non-prescription drugs by university’s students. For example, investigating students’’ behavior towards reading the drug information leaflets. Recently, he developed and evaluated an Educational Intervention designed for modifying university students’ practice, knowledge, awareness and attitude in favor of responsible self-medication.
Abstract:
Background: Use of non-prescription drugs (NPD) among university students is a serious public health issue. Previous study has reported that generally, a sizeable proportion of consumers do not read the drug information leaflet (DIL) before using NPD. However, few studies have identified the risk associated with not reading drug information leaflet before using NPD. There are no extensive studies, which measured the prevalence and identified the risk associated with not reading DIL among university students. Therefore, we attempted to fill the gap in the literature.
Methodology: A cross-sectional survey-based study was conducted from January to April 2014, among 2875 students in three randomly selected UAE universities. A structured and validated questionnaire was used to collect the responses of the students. SPSS version 20 was used to analyze the data.
Results: More than half (1348; 57%) of participants reported using of Oral NPD. Of 1348 participants reported using Oral NPD, one quarter (1348; 22.2%) of Oral NPD was classified as incautious Oral NPD usage as they did not read the DIL while using the medication for the first time. This study has identified 10 risk factors for incautious Oral NPD use. Participants with age group of 21 years and older (OR=0.554, 95% CI: 0.373-0.823) (p<0.001), female (OR=0.339, 95% CI:0.236-0.486) (p<0.001), and students from medical schools (OR=0.619, 95% CI: 0.435-0.882, p value=0.008) had lower odds of being incautious users compared to lower age group, males and students from non-medical schools. Furthermore, participants with a polypharmacy behaviour had higher odds of being incautious Oral NPD user than monopharmacy users (OR=1.400, 95% CI: 1.030-1.02) (p<0.001).
Conclusion: There a few incautious Oral NPD use among university students, but it is a serious issue when it comes to medical students. There is a need for raising awareness among all medical students to motivate them to be cautious users because they are going to be the future healthcare providers. Further studies are required to explore other risk factors.
Young Chul Kim
Seoul National University, South Korea
Title: Protective effect of Betaine against Galactosamine-induced acute hepatic injury in rats
Biography:
Young C Kim is a Professor of Toxicology at Seoul National University, College of Pharmacy, since 1986. He received his MS and PhD from Purdue University and completed Post-doctoral research at the National Institute of Environmental Health Sciences (NIEHS), NIH, USA. He has published more than 100 papers in reputed journals. He is a recipient of several prestigious international and national awards including the Thieme Most Innovative Original Paper Award at GA, Society for Medicinal Plant and Natural Product Research, and the Korean Teachers’ Award.
Abstract:
Statement of the Problem: Galactosamine (GalN) is a potent hepatotoxicant that inhibits RNA and protein synthesis via depletion of uridine nucleotide in the liver. Earlier studies suggested that some endogenous sulfur-containing substances, particularly glutathione (GSH) and/or S-adenosylmethionine (SAM), might antagonize the induction of liver injury by GalN. In this study, we determined the effect of betaine, a methyl donor used for remethylation of homocysteine to methionine, against GalN-induced acute liver injury in association with alterations in the metabolomics of sulfur-containing amino acids and related substances in the liver.
Methodology: Male Sprague-Dawley rats received betaine (1% in drinking water) for 2 wk prior to GalN challenge (400 mg/ kg, ip). Rats were sacrificed 24 h later for the assay.
Findings: GalN treatment elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and sorbitol dehydrogenase (SDH) activities significantly, and these changes were blocked by betaine supplementation. Histopathological examination revealed extensive multifocal necrosis with macrophage infiltration in liver of the GalN-treated rats, which was also inhibited by betaine supplementation. GalN treatment increased methionine, but not SAM levels in the liver. Betaine supplementation further increased the hepatic levels of methionine, SAM, and methionine adenosyltransferase (MAT) activity. Hepatic GSH contents were not altered by betaine or GalN. GalN treatment elevated ornithine and spermidine, but decreased putrescine levels in the liver, suggesting that the metabolic conversion of ornithine to putrescine was impaired. Betaine supplementation increased hepatic putrescine and spermidine significantly, but ornithine levels were unaltered. LDH leakage increased progressively for 24 h after GalN treatment in H4IIE cells, which was inhibited almost completely by betaine or SAM addition.
Conclusion & Significance: The results suggest that the hepatoprotective effect of betaine against GalN-induced liver injury may be associated with an enhancement of polyamine biosynthesis via induction of MAT activity and SAM availability in the liver.
Arik Dahan
Ben-Gurion University of the Negev, Israel
Title: The complexity of intestinal permeability and its implications on oral drug absorption and bioavailablity
Biography:
Arik Dahan is an Associate Professor of Pharmaceutics and Biopharmaceutics at the Department of Clinical Pharmacology and the School of Pharmacy, Ben-Gurion University of the Negev in Beer-Sheva, Israel. He is also an Adjunct Professor of Pharmaceutical Sciences at the College of Pharmacy, University of Michigan, USA. He received his PhD (2007) from the Hebrew University of Jerusalem. From 2007 until 2009, he was a Post-Doctoral Research Fellow at the University of Michigan College of Pharmacy with Professor Gordon Amidon. His research interest is the integration of up-to-date molecular and cellular mechanistic investigations of drug disposition in the context of the human body, in order to enable successful drug delivery and therapy. In implementing this molecular biopharmaceutical approach to ADME research, he is seeking to enable mechanistic-based successful solutions to drug delivery, especially (but not only) oral, in challenging scenarios e.g. low-solubility, low-permeability, efflux transport, extensive metabolism, poor site targeting, various pathophysiological conditions (e.g. obesity, inflammatory bowel disease), and pediatrics patient care. He has authored over 70 top-notch journal papers, and contributed chapters to 7 books.
Abstract:
In this lecture, regional-dependent intestinal permeability will be discussed, including dissolution aspects, as well as pathophysiological conditions. Permeability is location dependent, and pertains to each point throughout the gastrointestinal tract. A drug may exhibit significantly different intestinal permeability not only between the small and large intestine, but even within the small intestine, i.e. between the proximal jejunum and the distal ileum. The asymmetrical pH profile throughout the small intestine may be the underling mechanism for such segmental-dependent permeability of certain ionizable drugs. An asymmetrical expression pattern of different transporters throughout the intestinal tract may also cause such regional-dependent permeability. Asymmetrical intestinal enzymes expression may significantly influence the systemic bioavailability of a drug, although not necessarily affect the permeability. In these cases, rapid vs. sustained dissolving drug products may result unexpectedly different systemic drug levels. In conclusion, it is prudent to consider the intestinal permeability pattern when deciding on a certain dissolution profile.
Tuba Aydin
Agri Ibrahim Cecen University, Turkey
Title: Inhibition effects of Tarragon (Artemisia dracunculus L.) extracts and its metabolites against the carbonic anhydrase I and II isozymes
Biography:
Tuba Aydin is currently working as an Assistant Professor in the Faculty of Pharmacy at the Agri Ibrahim Cecen University, Turkey where she has been a faculty member since 2013. She completed her PhD at Ataturk University, Turkey. She has expertise in isolation and characterization of phytochemicals from natural products.
Abstract:
Tarragon, Artemisia dracunculus L. is a small shrub and perennial plant species. It spreads in Japan, India, Iran, Europe, North America and China. The plant has several medicinal properties. It used in making vinegar and salad. In this study, five metabolites were isolated from dichloromethane extract from tarragon and their the chemical structure was characterized as anethole (1), β-stigmasterol (2), herniarin (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4) and (2E,4E)-1- (piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (5) by IR, 1D and 2D NMR spectroscopic methods. Enzyme inhibition activities of ethanol, dichloromethane, n-hexane and methanol extracts of A. dracunculus L. and all of the pure metabolites were investigated against human carbonic anhydrase I and II isoenzymes. Enzyme inhibition effects of the extracts and pure metabolites were evaluated by comparison of their IC50 values for the first time in this study. Our results showed that the extracts and the pure compounds of A. dracunculus L. were found to be strong inhibitor against the human carbonic anhydrase I and II isoenzymes. The compounds and extracts were showed in the range of 8.65-486.2 μM of IC50 values for Carbonic anhydrase I and II.
Hussam AS Murad
King Abdulaziz University, Saudi Arabia
Title: Impact of combined inhalation of Roflumilast or formoterol plus fluticasone on matrix metalloproteinase-9 and its inhibitor in ovalbumin-asthmatic mice
Biography:
Hussam Murad worked as a Professor at Pharmacology and Clinical Pharmacy Departments in a number of universities in Egypt and Saudi Arabia. He has an experience of about 25 years in teaching and research. He has worked in 10 research projects as a Principal Investigator and as a first Co-investigator in another four. He has got funds from King Abdulaziz City for Science and Technology (KACST), Riyad, SA, and Deanship of Scientific Research, King Abdulaziz University (KAU), Jeddah, SA. He received the award of scientific publication from KAU, in 2015 and in 2017.
Abstract:
Statement of the Problem: In a recently-published work, we concluded that co-inhalation of roflumilast+fluticasone more significantly improved inflammatory and histopathological changes than co-inhalation of formoterol+fluticasone in ovalbumin-asthmatic mice. The matrix metalloproteinase-9 (MMP-9) is the principal MMP involved in pathogenesis of asthma, and thus its inhibition could be beneficial to protect against airway inflammation and remodeling. This study was designed in ovalbumin-asthmatic mice to investigate effects of inhaled roflumilast and formoterol alone or combined with fluticasone on levels of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF).
Methodology & Theoretical Orientation: Asthma was induced in female BALB/c mice by ovalbumin sensitization and challenge. In addition to the normal control (NC) group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n=8): positive control (PC), vehicle-treated, and five drug-treated groups. Treatments (μg/kg) were given as 15 min-inhalation once/day for seven days as follows: roflumilast (R, 500), formoterol (Fo, 50), fluticasone (F, 1000), roflumilast+fluticasone (R+F, 500+1000), and formoterol+fluticasone (Fo+F, 50+1000).
Findings: The PC mice showed significant increases of the levels of MMP-9 and TIMP-1 in the BALF compared to the NC group. All treatments (except formoterol) significantly decreased these ovalbumin-induced changes mainly with the R+F group which showed a non-significant difference from the NC group. The combinations were significantly different from monotherapies and the R+F group was significantly different from the Fo+F group.
Conclusion & Significance: Co-inhalation of roflumilast+fluticasone more significantly improved the BALF levels of MMP- 9 and TIMP-1 than co-inhalation of formoterol+fluticasone in the ovalbumin-asthmatic mice. Recommendations of adding inhaled roflumilast to inhaled corticosteroids could be beneficial in treatment of asthma due to its antiinflammatory and antifibrotic effects.