Dr. Anil Kumar, Postdoctoral Fellow, The Faculty of Chemistry, University of Warsaw, Poland | Department of Chemistry

Dr. Anil Kumar, Postdoctoral Fellow, The Faculty of Chemistry, University of Warsaw, Poland

Abstract: Polymorphism, the phenomenon of existence of a compound in multiple structural forms, is not uncommon in biologically active compounds and it has remained as one of the critical issues in drug development processes. Moreover, controlling polymorphism is a serious issue and it has paramount importance in the area of pharmaceuticals. While improving physicochemical properties of bioactive molecules has been a prime focus of the pharmaceutical chemists, not much efforts have been put towards the improvement of their potency via polymorphic modifications. However, the identification of polymorphs warrants careful screening of crystals and use of appropriate characterization techniques. In this thesis, we considered a few derivatives of 5-arylidene-2-aminothiazolidinones, the known anticancer agents and also some quinolone amide derivatives, the known antitrypanosomal agents, to discover polymorphism in them. We investigated the in-crystal, in-solution, and also in-silico properties of the polymorphs to correlate with their structure and bioactivities. Our results suggest that the bioactivities of polymorphs are governed by their molecular conformation. Further, for some of these polymorphs, to highlight the differences and similarities, we performed quantitative and qualitative analyses of electron densities derived using multipole modeling of high-resolution X-ray diffraction data. Furthermore, the electron density analysis was complemented with the reduced electron density based non-covalent interaction analysis to probe the root for the diversity in binding affinities of the polymorphic anticancer agents against its target human gamma-enolase.

Email Id: ak803@snu.edu.in

Profile Summary: 

Ph.D. dissertation, Shiv Nadar University 2022 " On the Potency of Polymorphic Bioactive Molecules: Insights from Accurate Analysis of Electron Density Distributions"

List of publications (included in the thesis):

1.  A. Kumar, J. Chauhan, K. D. Dubey, S. Sen and P. Munshi*, “Tuning Potency of Bioactive Molecules via Polymorphic Modifications: A Case Study” Mol. Pharmaceutics 202219, 1008−1018.

2.    A. Kumar, J. Chauhan, K. D. Dubey, S. Sen, P Munshi*, "Importance of Polymorphism in Improving the Potency of Bioactive Molecules" Acta Cryst.  2021A77, C891.

3.   A. Kumar, B. Mohanty and P. Munshi*, “Probing Diversity in Binding Affinities of Polymorphs of an Anticancer Agent against Human Gamma-Enolase - A Quantum Crystallographic Perspective” (under revision).

List of publications (not included in the thesis):

4.  S. Dutta, A. Kumar, P. Munshi*, “Understanding the Proton Tautomerism Mechanism in Organic Molecular Ferroelectrics: Insights from Quantum Crystallography” Acta Cryst.  2021A77, C913.

 

Research Advisor - Prof. Parthapratim Munshi

 

Research Type: 
Graduate