DOCKING SIMULATION OF 1,2,3-TRIAZOLO-INDOLE-2-CARBOXYLATE DERIVATIVES AS POTENTIAL HER2 INHIBITORS FOR BREAST CANCER THERAPY
DOI:
https://doi.org/10.36526/jc.v8i2.7201Keywords:
Molecular docking, Breast Anticancer,1,2,3-Triazolo-Indole-2-Carboxylate, ADMET, HER2Abstract
HER2 is a tyrosine kinase receptor involved in cell proliferation, differentiation, and survival. Its overexpression promotes cancer progression and therapeutic resistance, indicating the need for new HER2 inhibitors. In this study, twelve 1,2,3-triazolo-indole-2-carboxylate derivatives were evaluated as potential HER2 inhibitors using in silico approaches. Drug-likeness was analyzed using SwissADME, ADMET properties were predicted with pkCSM, and molecular docking was performed using MOE. Docking analysis indicated that several compounds exhibited strong binding affinity toward HER2, with compounds 6b, 6c, 6d, 6e, and 9a identified as the most promising candidates. Among them, compound 6d showed the most balanced profile, combining strong binding affinity, favorable interactions comparable to lapatinib, moderate aqueous solubility, high Caco-2 permeability, non-substrate behavior toward P-gp, and non-mutagenic properties. ADMET evaluation revealed that all compounds complied with Lipinski’s rule and exhibited high total clearance. However, limitations were observed in distribution parameters (VDss, Fu, and BBB), potential hepatotoxicity, and inhibition of several CYP enzymes, except CYP2D6. Overall, compound 6d is proposed as a promising HER2 inhibitor candidate, although further in vitro and in vivo validation is required to improve safety and pharmacokinetic profiles.
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