6,11-Bisthia Steroidal Analogues: Synthesis, Characterization, and Evaluation of Antimicrobial-, Antituberculosis-, and Antitumor Activity

Abstract

Aims: Synthesis, characterization, antimicrobial-, antituberculosis-, and antitumor activity of a few 6,11-bisthiasteroidal analogues have been carried out. Methodology: Subsequent reaction of the mixture 3 with phenylhydrazine hydrochloride/hydrazine hydrochloride under reflux in ethanol afforded the pyrazole derivatives 4/5. The isoxazole moiety in compounds 6 was built up from 3 with hydroxylamine hydrochloride. The pyrimidine derivatives 7 and 8 were prepared from the diketoester mixture 3 with urea and thiourea respectively. The benzodiazepine derivatives 9 and 10 were prepared from the condensation of 3 with o-phenylenediamine and 1,2-diphenylethane-1,2-diamine, respectively. Results: Compound 10 showed higher bioactivity against Klebsiella pneumoniae and Escherichia coli than the standard, chloroamphenicol, and equipotent to clotrimazole in inhibiting the growth of Candida albicans. These compounds were screened for their cytotoxic activity against human colon tumor cell line (HCT116) and human cervical cancer cell line (HeLa). Compound 10 displayed the highest activity among the tested compounds with IC50 equal to 12 µM for HeLa cell, and 11 µM for HCT116 cell, respectively.  Again, compound 10 was found to be the most promising being active against M. tuberculosis (H37Rv) with MIC 7.5 µM. Conclusion: Compound 10 displayed better antimicrobial-, antituberculosis-, and antitumor activity than the other derivatives.