Molecular docking of potential cytotoxic alkylating carmustine derivatives 2-chloroethylnitrososulfamides analogues of 2-chloroethylnitrosoureas

Abstract

The objective of this work was the molecular modelling by bio-isostery of 2-chloroethylnitrosoureas CENU into 2-chloroethylnitrososulfamides CENS derived from Carmustine. We evaluated the pharmacodynamic profile of the new chemical class by studying molecular docking using innovative software. Good molecular docking scores were obtained through Auto-dock vina of the PyRx 0.8 software, the energy of the complexes formed (Target-Ligand) during the interaction varies from - 5,400 to -5,700 Kcal/mol, the total average between the 45 conformers is −5,213 Kcal/mol. The results were validated by Auto-dock vina 1.5.6 in collaboration with the Molecular Chemistry and Natural Substances Laboratory at the Meknes Faculty of Science - Morocco, a range of -4,900 to -5,100 Kcal/mol was noted for CENS complexes derived from Carmustine with the 2DND target, reflecting a better CENS chemical affinity to the biological target and the stability of the ligand-DNA complex, compared with the analogue reference Carmustine with a score of - 4,700 Kcal/mol. By superimposing the results of molecular docking, analysis of data from the study of electrophilia based on load transfer ECT and publications on CENS, we can predict that inter-strand crosslink is likely to occur between the Guanine dG22 of strand B and the Cytosine dC3 of strand A, located in the poly dA-poly dT segment end within the narrow minor groove of the DNA target (2DND). The molecular docking study was a preliminary approach to understand the therapeutic mode of action of CENS. Communicated by Ramaswamy H. Sarma