Green Synthesis of Pyrazole Linked Thiazole Derivatives With Enhanced Anti-Breast Cancer Activity: Water Extract of Banana Peel-Mediated Protocol, Anticancer Screening, Epidermal Growth Factor Receptor Inhibition, In Silico Absorption-Distribution-Metabolism-Excretion and Density Functional Theory Calculations.

The current research investigates the green and efficient water extract of banana peel (WEB) mediated synthesis of thiazole derivatives and their anticancer activity against the MCF-7 breast cancer cell line. A total of 10 novel thiazole derivatives were synthesized by green protocol and characterized by Fourier-transform infrared, proton nuclear magnetic resonance (1H NMR), carbon-13 (13C) NMR and mass spectral methods confirming the successful synthesis of the desired thiazole derivatives. A 3:1 ethanol-to-WEB solvent mixture was identified as optimal, achieving an 83% yield within 1 h. The synthesis protocol accommodates a range of aryl and halogen substitutions, allowing for flexibility in compound design and resulting in high yields (75-88%) across diverse derivatives. Compound 4e, bearing a methoxy group, emerged as the most potent candidate with a minimum inhibitory concentration (IC50) of 11.03 ± 1.047 µM, while compound 4c, featuring a chlorine substituent, also showed strong activity with an IC50 of 13.36 ± 1.21 µM. The structure-activity relationship analysis indicated that both electron-donating and electron-withdrawing groups significantly influence anticancer potency. Molecular docking studies with epidermal growth factor receptors revealed that compound 4e has the highest binding affinity, with a docking score of -6.98 kcal/mol, surpassing the standard drug Gefitinib (-6.45 kcal/mol). Density functional theory study revealed electronic, chemical and biological characteristics of 4e through frontier molecular orbital, molecular electrostatic potential and global descriptors. Absorption-distribution-metabolism-excretion analysis suggested favourable drug-like properties for most compounds. These findings highlight the WEB-mediated synthesis as a valuable approach for developing bioactive thiazole derivatives with potential as anticancer agents.