Reaction of 7α-bromo-6-nitrocholest-5-enes with hydrazine: Formation of steroidal pyrazolines and molecular docking against SARS-CoV-2 omicron protease.

ABSTRACT

The present work reports simple and effective protocol for preparing 6α-nitro-5α-cholestano[7α,5-cd] pyrazolines (4-7) by the reaction of 7α-bromo-6-nitrocholest-5-enes (1-3) with hydrazine hydrate under reflux [the substrate (2) gave products (5) and (6) and the later on acetylation with AC2O/Py gave (7)]. In the case of reaction of 3ß-hydroxy analogue (3) with hydrazine, however, 6α-nitro-5α-cholestano [3α,5-cd] pyrazoline (8) and 6α-nitro-3ß, 5-oxido-5ß-cholestane (9) were obtained. The probable mechanism of the formation of pyrazolines has also been outlined. In the current pandemic coronavirus disease 2019 scenario, the in-silico study was performed with reactants (1-3), their products (4-9) against SARS-CoV-2 omicron protease (PDB ID7T9L) for knowing significant interactions between them. Docking results give information that both reactants and products have binding energies ranges from -5.7 to 7.7 kcal/mol and strong interactions with various hydrophilic and hydrophobic amino acids such as ASP, PRO, PHE, SER and LEU which are significant residues playing important role in SARS-CoV-2 Omicron main protease (Mpro).