Microwave-assisted one pot synthesis, characterization, biological evaluation and molecular docking studies of steroidal thiazoles

In the present manuscript, a series of steroidal thiazole derivatives (4-6, 8) have been synthesized in efficient manner by one step reaction methodology employing microwave irradiation. The synthesis involves the reaction of steroidal ketones (1-3, 7) with thiosemicarbazide and phenacyl bromide. Structural assignment of the products was confirmed on the basis of IR, H-1 NMR,C-13 NMR, MS and analytical data. The synthesized compounds were screened for in vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. In addition, the products 4-6, 8 were also tested for pBR322 DNA cleavage activity, genotoxicity, reactive oxygen species (ROS) production and RBC hemolysis. Molecular docking analysis was carried out to validate the specific binding mode of the newly synthesized compounds into the active site of DNA. Docking showed formation of more stable complexes of compounds 4 and 8 with the free binding energies - 8.1 and - 8 kcal/mol, respectively. Hence, it could be suggested that the steroidal compounds bearing a core thiazole scaffold would be a potent biological agent. (C) 2016 Elsevier B.V. All rights reserved.