Basic Informations

C.V

Dr. Ahmed H. Abdelazeem, an associate professor of medicinal chemistry and drug design, graduated from Faculty of Pharmacy, Cairo University (1997-2002). He received his Ph.D. degree in Medicinal Chemistry through a channel system between School of Pharmacy, University of Mississippi, USA and Beni-Suef University, Egypt with a thesis on design and synthesis of novel sigma receptors ligands for treatment of psychostimulant abuse. He is working as an assistant Professor of Medicinal Chemistry at Faculty of Pharmacy, Beni-Suef University. Currently, he is working temporarily for College of Pharmacy, Taif University, KSA. He is involved in teaching all Medicinal Chemistry and drug design courses to undergraduate pharmacy students as well as supervising many postgraduate students’ theses. He is interested in design and synthesis of new chemical entities of anticipated anticancer or anti-inflammatory activities using recent molecular modeling approaches and studying their molecular mechanisms of action as well. He has several publications in prestigious peer-reviewed journals in addition to two US Patents.

Research Interest

1)      Multistep organic synthesis of novel ligands of biological interest (CNS drugs, anticancer and anti-inflammatory agents).

2)      Molecular modeling including ligand- and structure-based drug design approaches.

3)      Virtual screening techniques for discovery of new hits for various drug targets.

Master Title

Molecular modeling and synthesis of some substituted Acridine derivatives of anticipated antitumor activity

Master Abstract

In search for new antitumor agents and encourage by marked cytotoxic activity of acridines, it is of interest to synthesize and screen the potential antitumor activity of some new acridine derivatives. The thesis consists of the following parts: 1- Introduction This section contains a brief literature review on different classes of antitumor agents relative to their mechanism of action as well as antitumor activity of acridine derivatives. 2- Aim of the work This part presents the aim, rationale and molecular modeling study upon which the newly synthesized compounds are designed and synthesized. 3- Discussion It deals with the discussion of the experimental methods adopted for synthesis of designed compounds. Schemes 1, 2, 3 and 4 illustrate the synthetic pathway followed for preparation of designed compounds. 4- Experimental This part includes practical procedures for synthesis of designed and known compounds. Physical, spectral and microanalytical data are included in this part. In the present investigation, 13 known starting compounds, 8 novel intermediates and 40 novel final compounds belonging to 4 series of new acridine derivatives of anticipated antitumor activity have been synthesized.

PHD Title

Design and synthesis of substituted heterocycles for the treatment of psychostimulant abuse

PHD Abstract

In recent year, significant advances have been made in understanding sigma (s) receptors, and countless novel ligands have been developed. s Receptors are now recognized as unique binding sites with a distinct ligand selectivity patterns and specific anatomical distributions from other receptors. Within the established pharmacological profile of cocaine, s receptors have gained attention as potential targets for drug discovery of anticocaine agents. It was proven that cocaine and other spychostimulants interact with s receptors, providing logical and validated targets for the development of medications to counteract their actions. Several classes of structurally unrelated compounds interact with s receptors, but unfortunately ligands in general showed a low order of selectivity. In an effort to find highly selective s receptor ligands, we designed two series of compounds using phthalimide and benzoxazinone heterocycles as building blocks. The second part of this research focused on enhancing the metabolic stability of the previously reported CM156 (172) which has the highest affinity and selectivity for s receptor, but it suffered from a short half-life profile (4.62 min). In doing so, we designed a small series of analogs to study the structure-metabolism-relationships by blocking potential vulnerable sites of metabolism as well as studying the effects of these structural modifications on structure-affinity-relationships. Finally, we developed two 3D models using PHASE program implemented in Schrödinger software to further investigate the structural features required for the activity and selectivity of both s subtypes ligands. The in vitro radioligand binding assays revealed most substitutions are being well tolerated and identified AZ-66 (253) has a high affinity (Ki, s1= 0.31 nM, s2 = 1.76 nM) ligand with potential for improved metabolic stability. AZ-66 was then subjected to in vitro liver microsomal assays which revealed a significant improvement of its half-life (115.5 min). Also, it was found that AZ-66 has the ability to significantly attenuate the actions of cocaine and methamphetamine in vivo.