Medicinal Chemistry

An Alternative Approach to Computational Peptidology Based on Conceptual DFT and Empirical Bioactivity Scores

Abstract

Norma Flores-Holguín, Juan Frau and Daniel Glossman-Mitnik

This work presents the results of a study of the global and local chemical reactivity of the antineoplastic Elisidepsin and Plitidepsin marine drugs based on the calculation of descriptors coming from Conceptual DFT for their consideration as a tool to explain the molecular interactions, and as a useful complement to those approximations based on Molecular Docking. The knowledge of the values of the global and local descriptors of the molecular reactivity of the Elisidepsin and Plitidepsin molecules obtained through our proposed methodology could be useful in the development of new drugs based on these compound or some analogs relying in the chemical interaction between these peptides and their biological receptors of protein kind. It can be concluded that the Conceptual DFT approximation to the global and local chemical reactivity based on the descriptors can provide interesting information for the consideration of both molecules a potential drugs. This is complemented with a study on AGEs inhibition by comparison with the usual molecular systems considered for that task. Finally, the bioactivity scores for Elisidepsin and Plitidepsin are predicted by considering similarity searches of compounds with structures that can be compared to those that are being studied whose pharmacological properties are well known.