title: Microwave-assisted one pot synthesis, characterization, biological evaluation and molecular docking studies of steroidal thiazoles.
abstract: 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,1H NMR,13C 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 -8kcal/mol, respectively. Hence, it could be suggested that the steroidal compounds bearing a core thiazole scaffold would be a potent biological agent.
authors.affiliation: Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Asif
authors.affiliation: Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Abad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Atif
authors.initials: A
authors.lastname: Zafar
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Farhan
authors.affiliation: Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Hena
authors.initials: H
authors.lastname: Khanam
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: S M
authors.initials: SM
authors.lastname: Hadi
authors.affiliation: Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: shamsuzzaman9@gmail.com.
authors.lastname: Shamsuzzaman
mesh_terms: D020552:Comet Assay; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008872:Microwaves; D062105:Molecular Docking Simulation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013057:Spectrum Analysis; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology; D014783:Viscosity
chemical_list: D017382:Reactive Oxygen Species; D013844:Thiazoles
keywords: Comet assay; Hemolysis; Molecular docking; Nuclease activity; Thiazole