Toward A Chemical Genetics Approach: Privileged Diversity Oriented Organic Synthesis of Novel and Constrained Compound Collections as Lead Drug Candidates
Taleb H. Al-Tel
Sharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, P.O.Box 27272, Sharjah, United Arab Emirates
Normal biological processes generally rely on a finely tuned network of dynamic macromolecular interactions that allow signals to transfer throughout the cell. Miss-regulation of these signaling cascades often ends in disease states. For example, miss-regulated protein-protein interactions lead to unchecked cellular signaling in multiple forms of cancer, immunological disorders and neurodegenerative disorders. To modulate the activity of these signaling proteins in a disease state, efforts are directed towards constrained and privileged small molecules ligands that bind to a particular catalytic or active site, as a starting point in a drug discovery campaign. The exploration of such an approach requires a good starting chemical point. The engine powering of such a point is driven by novel synthetic strategies that lead to a chemical space of skeletally diverse and privileged molecular architectures that is capable of interrogating unexplored biological space. In this regard, stereochemical complexity is important since many biological processes are critically dependent on protein-protein interactions, and many of the small molecules known to disrupt these interactions are structurally complex natural products. Therefore, privileged diversity oriented synthesis is a prominent approach, especially in cell- or organism-based screens where small privileged molecules are screened in search of a specific phenotype. In this seminar, I will be describing our efforts in designing diverse stereochemically enriched macrocylic compound collections (medium and large sized ring systems) possessing privileged architectures that represents the basic core of many biologically significant compounds (Figure 1). Further, preliminary anticancer and antimalarial activities of these motifs will also be presented.
Protein kinase C (PKC) modulator-Anticancer
Figure 1. Representative Examples of Bioactive Compounds Pairing Privileged Skeleton.
Taleb Al-Tel received his BS in Chemistry and Chemical Technology in 1987, MS in Natural Product Chemistry in 1990 from the faculty of Chemistry, Jordan University and Pennsylvania State University, and PhD in 1995 from Tuebingen University-Germany under Professor Wolfgang Voelter (Design and Synthesis of Oxaring Systems from Carbohydrates as Lead Drug Candidates) followed by an NIH Postdoctoral Fellowship under the supervision of Professor Scott Sieburth, (Synthesis of Antiviral Lead drug candidates) at State University of New York, Stony Brook, NY. In 2003 he was appointed as a visiting associate professor at Duke Chemistry Department, North Carolina. Al-Tel joined Transtech Pharma-USA A Drug Discovery and Development Company in 2004-2007 as principal scientist and promoted to Team Leader for Drug discovery groups (antiviral, anticancer, Obesity and Alzheimers). In 2007 He joined the college of pharmacy-University of Sharjah as associate professor of organic medicinal chemistry then promoted to Professor in 2013.
Scientific Contributions include over 60 invited lectures, presentations, keynote Speaker and a co-author of more than 65 publications in leading journals; inventor on a one US-issued patent.
Major Awards include: The German Award for the Exchange of Scholars (DAAD); Abdel Hameed Shoman Prize for Young Arab Researchers (1999); Islamic Development Bank Award (2003); Fulbright Award (2003/2004); The Chemist of the Year Award-2005, TransTech Pharma-USA.
Scientific and Professional Activities include Advisory Board member of Mini Reviews on Medicinal Chemistry, Open Journal of Natural Products, American Chemical Society-member.
Academic Appointments: Assistant and then Associate Professor of Organic Medicinal Chemistry at An-Najah University; Duke University; University of Sharjah. Invited Visiting Professor at many Schools including, Tuebingen University-Germany, Molecular Pharmacology Research Institute-Berlin, Ecole-Normale Superior-Paris. Then Professor of Organic Medicinal Chemistry at the College of Pharmacy-UOS; Director-RIMHS.