Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors

ÇEVİK U. A., SAĞLIK B. N., OSMANİYE D., LEVENT S., Cavusoglu B. K., KARADUMAN A. B., ...More

ARCHIV DER PHARMAZIE, vol.353, no.5, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 353 Issue: 5
  • Publication Date: 2020
  • Doi Number: 10.1002/ardp.202000008
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Eskisehir Osmangazi University Affiliated: No


Aromatase is involved in the biosynthesis of estrogen and thus is a critical target for breast cancer. In this study, to identify new aromatase enzyme inhibitors, seven 3-[4-(5-methyl-1H-benzo[d]imidazol-2-yl)phenyl]-6-(substituted phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives were synthesized. First, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the inhibitory activity of the synthesized compounds on the MCF-7 cell line. The aromatase inhibitory activity was determined for the active compounds 5b, 5c, 5e, and 5g on the MCF-7 cell line. Compound 5g showed significant aromatase inhibitory activity (IC50 = 0.037 +/- 0.001 mu M). Interestingly, this compound, which bears a difluoro substituent at positions 2 and 4 of the phenyl ring, displayed the most potent aromatase inhibitory activity without significant cytotoxicity to a normal healthy cell line (NIH3T3). Furthermore, the interactions between the best active compounds and the active site of the enzyme were analyzed through a docking study. The results of this study determined that benzimidazole-triazolothiadiazine derivatives are promising compounds that should be further developed as a novel class of aromatase inhibitors.