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In order to obtain potential anticancer agents, hybrid compounds have been synthesized by coupling thiazolidinone and pyrazole scaffolds. Among the synthesized compounds, 2-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl thiazolidin-4-one (4a) was found to be the most potent based on a docking (−9.307) and binding scores (−66.46), along with good ADME parameters. In vitro anticancer activity of compound 4a shows a maximum inhibition against lung cancer (NCI-H23) cell lines with a moderate inhibition rate of 31.01%. Molecular docking studies revealed that these hybrid compounds bind well to the active site of peroxisome proliferator-activated receptors-gamma (PPAR-gamma). Doxorubicin was used as a positive control. It can be concluded that 4a having pyrazole-thiazolidinone ring systems has the potential to be developed as an anticancer agent. [ABSTRACT FROM AUTHOR]

In the present study, a novel series of new furanone-based benzothiazole derivatives (4a-j) were synthesized from 4-(benzo[d]thiazol-2-yl)-4-oxobutanoic acid (3) as potential anticancer agents. In vitro cytotoxicity against three human cancer cell lines (A549, MCF7, and DUI45) revealed substantial activity. Di-substituted compound, 4i emerged as a promising anticancer compound which showed IC50 values of 7.2 ± 0.5, 6.6 ± 1.4, and 7.3 ± 0.1 µM against A549, MCF7, and DUI45 cell lines, respectively. Four compounds 4c, 4e, 4f, and 4i evaluated for their acute toxicity were found to be non-toxic on the two vital organs (liver and heart). Further, these compounds were found to be more efficient and less hepatotoxic in comparison to standard drug doxorubicin. Molecular docking studies carried out with VEGFR-2 revealed compounds 4a and 4i as potential VEGFR-2 kinase inhibitors. In silico ADME evaluation was carried out to estimate and predict drug-likeness. Compound 4i demonstrated the best ADME parameters. Based on the results of docking analyses, ADME, and in vitro cytotoxicity, compound 4i is identified as the lead compound for further development of anticancer agents. [ABSTRACT FROM AUTHOR]