Synthesis, Characterization And Biological Activities Of Some Novel Acylthiosemicarbazides,1,3,4-Thiadiazole/Oxadiazole Derivatives Containing Benzimidazole Moiety

1. Forty new target compounds, including twenty novel acylthiosemicarbazides (7a~7t),eighteen2,5-disubstituted-1,3,4-thiadiazoles (8a~8r) containing benzimidazole moiety andtwo2,5-disubstituted-1,3,4-oxadiazoles containing glucopyranosyl (9a~9b) weresynthesized by o-phenylenediamine and aryloxyacetic acids as the starting materials via aseries of reactions. The structures of the target compounds were characterized by IR,1HNMR, MS and elemental analyses.2. Using1H,13CNMR,2DNMR (HSQC HMBC,1H-1HCSY) technology, the targetcompound was proved that the acylthiosemicarbazides7at room temperature, DMSOexist two isomers chain and ring type in the try two isomers and chain isomerpredominates, content is75%~100%.3. The1H and13CNMR,2DNMR techniques of target compounds9a1H,13C chemical shiftof ownership. Therefore, compound9b1HNMR for the belonging4. Using relevant software for the synthesis of target compounds the oral bioavailability ofparameter calculation, the calculation results show that the vast majority of the targetcompounds have good oral bioavailability.5. The newly synthesized target compounds (7a~7t,8a~8r) were screened for their biologicalactivities.①. The assay results of inhibitory activity against Cdc25B phosphatase show thatsome of the compounds (7n、7q、7r、7s、8d、8f、8g、8j、8m) exhibit high activity at5μg/mL and the IC50are in the range of5.81±1.25~1.48±0.08μM. The best inhibitor iscompound7q with IC50=1.48±0.08μM. The results suggest that the target compoundshave good anticancer activity.②. The assay results of inhibitory activity against PTP1B exhibit that eleven titlecompounds (7i、7o、7t、8d、8f、8g、8j、8l、8m、8q、8r) show high activity at5μg/mLand the IC50are in the range of7.75±1.71~1.29±0.16μM. The best inhibitor is compound8g with IC50=1.29±0.16μM. The results showed that the target compounds have goodantidiabetic and obese activity.③. The results of inhibitory activity against DPPH (antioxidant) assay indicateseveral acylthiosemicarbazides compounds exhibit weak activity at5μg/mL and the bestinhibitor is compound7c with inhibitory rate45.29%.1,3,4-Thiadiazole compounds 8a~8r have no antioxidant activity.④. The assay results of inhibitory activity against DPP-IV show that most targetcompounds have weak inhibitory activity at6.5μg/mL and the best inhibitor is compound7s with inhibitory rate21.55%.6. In conclusion, the assay results of biological activity show that most of the targetcompounds show higher inhibitory activity against Cdc25B phosphatase and PTP1B.These activities make them attractive candidates for further assessment in anticancer,diabetes and obesity agents. In addition, some of the target compounds have weakinhibitory activity against DPPH and DPP-IV.