Biological Evaluation of Indole Appended Triazolothiadiazepine Conjugates as Potent Anticancer Agents

Abstract

Background: Cancer is one of the major health and socio-economic problems of the world even though extensive progress has been made in terms of early diagnosis and cure. The research for new anticancer drug development with more effective treatment is a field of utmost importance in current drug discovery. Method: Molecular Hybridization (MH) strategy has been adapted for the rational design of new ligands, where pharmacophoric sub-unities in the molecular structure of two bioactives will lead to the design of new hybrid architectures. All the synthesized compounds (3a-z) were evaluated in HeLa and MCF-7 cell lines for their anticancer activity and compared against H9C2 normal cells. Results: As expected, among the tested compounds, 3a, 3d, 3g, 3j, 3m and 3s exhibited highest activity with GI50 value of 1.72 µm, 2.10 µm, 4.26 µm, 2.43 µm, 5.11 µm and 4.34µm in HeLa cells and 1.86 µm, 2.50 µm, 5.20 µm, 4.40 µm, 6.14 µm and 5.30 µm in MCF-7 cells respectively. We also found that the compounds were non-toxic to H9C2 cells up to 20 µM. Conclusion: Preliminary structure-activity relationship studies revealed that compounds with para-Cl substituted phenyl and 5-Cl substituted indole on diazepine ring proved to be more potent. Keywords: Indole analogues, chalcones, triazolothiadiazepines, molecular hybridization, cytotoxic activity, HeLa & MCF-7, SAR studies.