= 0.67, 0.53, and 0.40 μM, respectively, hence circumventing cancer resistance mechanisms. The most potent Compound 2h prompted apoptosis and necrosis at % G0-G1 phase in HCT-116 via the activation of caspase-3 and 8, with significant downregulation of anti-apoptotic protein Bcl-2. Additionally, Compound 2h markedly suppressed immunomodulatory proteins TNF-α and IL-6 levels by 80.9% and 88.2%, respectively, in comparison to dexamethasone (82.7% and 93.2%, respectively), which attenuates tumor-promoting inflammation, disrupting pro-survival signaling pathways and metastasis. In silico ADMET, toxicity, and molecular docking studies were performed; notably, the docking simulations generated an interesting hypothesis for potential direct binding to Bcl-2, an effect distinct from the experimentally observed downstream downregulation of its expression. The present results pave the way for further developing of 2h candidate as a multi-tyrosine kinases inhibitor toward colon cancer cells.
Ahmed et al. (Fri,) studied this question.