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The reaction of the appropriate α-haloketones or α-keto-hydrazonoyl chlorides with the corresponding bis(hydrazinecarbothioamide) in EtOH at reflux in the presence of a few drops of TEA produced good yields of novel bis-thiazoles linked to diphenyl ether as novel hybrid molecules. Furthermore, some novel bis-thiazoles were obtained in high yields by reacting 1,1′-(oxybis(4,1-phenylene))bis(2-bromoethanone) with the appropriate thioamide. Furthermore, by reacting bis(2-bromoethanone) with the appropriate 4-amino-3-mercapto-1,2,4-triazole derivatives in ethanol in the presence of TEA, novel bis(5,6-dihydro-s-triazolo[3,4-b]thiadiazines) linked to diphenyl ether moiety were obtained in good yields. Moreover, by reacting bis(2-bromoethanone) with the appropriate pyridinethiones in ethanolic sodium ethoxide at reflux, good yields of bis(thienopyridines) linked to diphenyl ether moiety were obtained. The structures of new compounds were confirmed using elements and spectral data. [ABSTRACT FROM AUTHOR]

A synthesis of novel bis-thiazoles, linked to quinoxaline as novel hybrid molecules, was accomplished in good yields by the reaction of the appropriate α-haloketones or α-keto-hydrazonoyl chlorides with the corresponding bis(hydrazinecarbothioamide) in ethanol/dimethylformamide (EtOH/DMF) at reflux in the presence of a few drops of triethylamine (TEA). The reaction of the appropriate thioamide with the corresponding bis(2-bromoethanone) yielded novel bis-thiazoles. Furthermore, by reacting bis(2-bromoethanone) with the appropriate 4-amino-3-mercapto-1,2,4-triazole derivatives, novel bis(5,6-dihydro-s-triazolo[3,4-b]thiadiazines) linked to quinoxaline moiety were obtained in good yields. The starting bis-thiosemicarbazone was obtained by reacting 1,1'-((quinoxaline-2,3-diylbis(oxy))bis(4,1-phenylene))diethanone with thiosemicarbazide in EtOH containing a few drops of acetic acid (AcOH) at reflux. On the other hand, the 1,1'-((quinoxaline-2,3-diylbis(oxy))bis(4,1-phenylene))bis(2-bromoethanone) was obtained from the corresponding bis(acetyl) derivative upon treatment with N-bromosuccinimide (NBS) in the presence of p-toluenesulfonic acid (p-TsOH), respectively. Structures of new compounds were confirmed using elemental analyses and spectral data. [ABSTRACT FROM AUTHOR]

• A series of novel bis-thiazoles coupled to benzofuran or benzothiazole moieties were synthesized. • Several analytical and spectroscopic techniques were used to characterize all of the products. • Cytotoxicity against three human tumor cell lines: hepatocellular carcinoma (HEPG-2), colorectal carcinoma colon cancer (HCT-116), and human breast cancer (MCF7) were investigated. • Enzyme inhibition and cell cycle apoptosis properties were investigated for the most active compound. • P53 and cyclinB1 gene expressions were also examined using Western Blot. • A molecular docking study of compound 6c revealed that it fits well and interacts with the active pocket of 4JPS related to pi3ka through various interactions. • Compound 6c proved to be a promising candidate as a highly effective pi3ka inhibitor and a strong anticancer candidate drug against various cancer cell lines. A molecular hybridization approach was used to construct and develop a variety of new bis-thiazoles coupled to benzofuran or benzothiazole moieties as anticancer drugs. The target compounds 6a-f and 7a-f were synthesized by reacting the respective bis-thiosemicarbazones 5a–f with bromoacetylbenzofuran or bromoacetybenzothiazole. Several analytical and spectroscopic techniques were used to characterize all of the products. Using the MTT assay, compounds 6a-f and 7a-f were tested for cytotoxicity against three human tumor cell lines: hepatocellular carcinoma (HEPG-2), colorectal carcinoma colon cancer (HCT-116), and human breast cancer (MCF7). The results showed that 6c and 7e had strong antitumor activity against HePG2, MCF7, and HCT-116, with IC50 values of 6.89, 9.94, and 12.67 µM for 6c and 8.37, 7.31, and 24.86 µM for 7e , respectively, when compared to the standard reference drug, doxorubicin (IC50 =5.50, 5.23 and 8.87 µM, respectively). The most active drugs' enzyme inhibition and cell cycle apoptosis properties were investigated further. Compound 6c 's apoptotic and necrotic properties were promising. P53 and cyclinB1 gene expressions were also examined using Western Blot to investigate changes in apoptosis and cell cycle-related protein expression. The results showed up-regulation of P53 and down-regulation of cyclinB1 and were found to be inconsistent with those obtained by chemotherapeutics sorafenib, fluorouracil, and methotrexate. Interestingly, the molecular docking study indicated that chemicals 6c, 6d , and 7e could all be lodged in the active pocket of the 4JPS enzyme via various interactions. [Display omitted] [ABSTRACT FROM AUTHOR]