New tetrazolopyrrolidine-1,2,3-triazole analogues as potent anticancer agents: design, synthesis and molecular docking studies.

Abstract

1,2,3-Triazole and tetrazole derivatives bearing pyrrolidines are found to exhibit notable biological activity and have become useful scaffolds in medicinal chemistry for application in lead discovery and optimization. We report design, synthesis and molecular docking studies of tetrazolyl-1,2,3-triazole derivatives (7a-i) bearing pyrrolidine moiety and evaluating their anticancer activity against four cancer cell lines viz. Hela, MCF-7, HCT-116 and HepG2. The structures of the new compounds were ascertained by spectral means IR, NMR: ¹H &¹³C and Mass spectrum. From the studies compounds7a and 7i exhibited significant anticancer activity against the Hela cell line with IC₅₀ = 0.32 ± 1.00, 1.80 ± 0.22 μM when compared to reference drug Doxorubicin (IC₅₀ = 2.34 ± 0.11 μM), whereas 7h, 7i, and 7b were found to be active against MCF-7, HCT-116 and HepG2 cell lines with IC₅₀ = 3.20 ± 1.40, 1.38 ± 0.06 and 0.97 ± 0.12 μM respectively. Notably 7a exhibited highest conventional hydrogen bondings TyrA:40, SerA:17, LysA:117, AlaA:146, Tyr218 with 3HB4and SerA:17, LysA:117, AlaA:146, TyrA:40 with 6IBZ and docking energy - 10.85, - 8.21 kcal/mol respectively. These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME. The results of the in vitro and in silico studies suggest that the tetrazole incorporated pyrrolidine-triazoles may possess the ideal structural requirements for further developing new anticancer agents.