Design and synthesis of Meldrum's acid based 7-azaindole anchored 1,2,3-triazole hybrids as anticancer agents†

Abstract

A series of Meldrum's acid, 7-azaindole and 1,2,3-triazole hybrids were synthesized and evaluated for their in vitro anticancer activity against five different cancer cell lines viz. MCF-7 (breast cancer), HeLa (cervical cancer), DU-145 (prostate cancer), HepG2 (liver cancer) and K562 (myelogenous leukemia cell). Among the series, compound 6b containing a 4-methyl substitution showed potent activity against HeLa cell line. Cell cycle analysis revealed that compound 6b induced cell cycle arrest at the G2/M phase and induced apoptosis. Apoptotic activity was further confirmed by Hoechst staining and Annexin V-FITC assay. Compound 6b has been found to exhibit higher activity in all four cell lines, with IC₅₀ values of 6.67 ± 0.39 μM, 4.44 ± 0.32 μM, 12.38 ± 0.51 μM and 9.97 ± 0.25 μM against MCF-7, HeLa, DU-145 and HepG2 cell lines respectively. Compounds 6m (9.68 ± 0.10 μM) and 6n (9.52 ± 0.38 μM), which have dimethoxy and trimethoxy substitutions, respectively, have demonstrated significant anticancer activity against HeLa cells compared to the other cells. The molecular docking study of ligand 6b against the crystal structure of EGFR and Mcl-1 scored notable binding energy values and displayed important interactions like H-bond, π–cation and other hydrophobic interactions.