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A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e, 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR. [ABSTRACT FROM AUTHOR]

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (4a-d), 1,3,4-thiadiazoles (6a-d), and pyrimidines (8a-d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53–69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations. [ABSTRACT FROM AUTHOR]