Design and synthesis of triazole-functionalized isatin hybrids with potent anti-proliferative action against triple-negative breast cancer MDA-MB-231 cell line: a hybrid pharmacophore approach

Differently substituted novel 1-(2-((aryl-4H-1,2,4-triazol-3-yl)thio)acetyl)indoline-2,3-diones have been synthesized, geometrically optimized, and examined for global reactivity indices through the DFT framework. The anti-proliferative potency of the triazole-endowed isatin hybrids has been evaluated against the TNBC cell line, MDA-MB-231, through MTT assay. The title compounds demonstrated promising anticarcinogenic action. Compound 4(iii) with 2-chlorophenyl substituent displays the best IC50 value of 0.73 mu M, although compound 4(vi) bearing 5-chloroisatin moiety showed maximum inhibition at 100 mu M concentration with an IC50 of 6.9 mu M. EGFR receptor, a potential TNBC target, is used in docking simulations to identify pertinent binding interfaces of the synthesized molecules within the receptor's active site. The outstanding docking result with binding scores between - 8.1 and - 9.5 kcal/mol demonstrates the notable EGFR inhibitory propensity of the examined hybrids. The synthesized entities have been investigated through ADMET screening to anticipate their drug candidature. The in vitro and in silico explorations project the novel isatin hybrids as efficient anti-breast cancer leads with tenable drug proclivity.