Synthesis of 4-Azaindole-Thiazolidine-2,4-Dione Coupled 1,2,3-Triazoles as EGFR Directing Anticancer Agents

Abstract

Herein, we synthesized some new 4-azaindole-thiazolidine-2,4-dione-1,2,3-triazole hybrids (6a-6n) via Knoevenagel condensation and copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) as key approaches. These hybrids were then screened for their in vitro anticancer activity against three human cancer cell lines like MCF-7 (breast), A549 (lung) and HepG2 (hepatocellular) using erlotinib as standard drug. Out of all, compounds 6a, 6k and 6m were found to be more active against all cell lines with IC₅₀ values <18 µM. As well, compounds 6a (IC₅₀ = 0.40 µΜ), 6k (IC₅₀ = 0.29 µΜ) and 6m (IC₅₀ = 0.18 µΜ) showed higher potency ininhibiting tyrosine kinase EGFR than the erlotinib (IC₅₀ = 0.41 µΜ). Further, molecular dockingof compounds 6a, 6k and 6 m on EGFR protein revealed that they have good binding energies with the target protein (−9.96 kcal/mol, −9.92 kcal/mol and −10.37 kcal/mol respectively) which were found to be supportive with the corresponding in vitro activities data.