Synthesis of New 1,4-Disubstituted 1,2,3-Triazole Hybrids: In Vitro Anti-Breast Cancer and Anti-EGFR Activity, and In Silico Molecular Docking Studies

Objective: Encouraged by previously developed 4-azaindole, thiazolidine-2,4-dione, and 1,2,3-triazole-based EGFR-targeting anti-breast cancer agents, our group aimed to design new 4-azaindole-thiazolidine-2,4-dione-1,2,3-triazole hybrids and evaluate their anti-breast cancer and anti-EGFR activities. Methods: As part of our ongoing work on the development of new anticancer agents, this study focused on the synthesis of hybrid molecules. The anti-breast cancer and anti-EGFR activities of the newly synthesized hybrids were assessed by IC50 measurements, and molecular docking studies were conducted using AutoDock Tools. Results and Discussion: Compound (VIIg) displayed greater anti-breast cancer activity against MCF-7 and MDA-MB-231 cell lines compared to the standard drug 5-Fluorouracil (5-FU). Compounds (VIIb) and (VIIh) exhibited higher potency against MCF-7 than 5-FU. Compounds (VIIb) and (VIIg) showed significant EGFR inhibition relative to the standard drug Erlotinib. Furthermore, compounds (VIIb), (VIIg), and (VIIh) demonstrated better binding energies and inhibition constants for EGFR (PDB ID: 4HJO) than Erlotinib. Conclusions: Compounds (VIIb), (VIIg), and (VIIh) exhibited potent anti-breast cancer activity, which was supported by their strong anti-EGFR activity.