Abstract:

In the quest for effective cancer therapeutics, the optimization of pharmacokinetics, toxicity profiles, and efficacy is crucial. This study introduces a novel series of 5-(substituted benzylidene)-2-(arylamino)-1,3-thiazol-4(5H)-ones, synthesized to explore their potential as anti-cancer agents. These compounds were specifically designed based on the promising anti-tumour activity of 5-arylidene-4-thiazolidinone derivatives, known for their efficacy against MDA-MB-231 (human breast cancer cell line). To assess these new thiazol-4-ones, we used sophisticated in silico methods to perform pharmacokinetic ADME predictions and molecular docking simulations. Our molecular docking studies utilized FlexX to compare the binding affinities of these compounds with known drugs: Gestrinone (targeting EGFR alpha for breast cancer), Vandetanib (targeting VEGFR-2), and KU0058948 (targeting Poly ADP ribose polymerase for ovarian cancer). These comparative analyses revealed significant interactions with these key cancer targets. In addition, ADME predictions were performed using the iLOG predictor from Swiss ADMET software, demonstrating favourable properties for absorption, distribution, and bioavailability. Interestingly, compounds with fluorine substitutions at positions 2 or 4 of the acylamino ring showed encouraging activity and satisfied Lipinski and Veber's rules-based drug-likeness requirements, indicating that they could make good candidates for therapeutics. Furthermore, these compounds showed low toxicity levels, enhancing their suitability for further development.

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