One-pot Synthesis And Biological Activities Of Benzimidazole-based Acylthiosemicarbazide,1,3,4-thiadiazole/Diacylhydrazine Derivatives

1. Twenty four novel acylthiosemicarbazide (VII),1,3,4-thiadiazole (VIII)/diacylhydrazine(IX) derivatives containing benzimidazole moiety were synthesized by2-aryloxymethyl-acethydrazide (IV) and isothiocyanate (VI) under ultrasonic irradiation and solid-liquidphase transfer catalysis. The important intermediates2-aryloxymethyl-acethydrazide (IV)were synthesized by o-phenylenediamine and aryloxy acetic acid as the starting materialsvia a series of reactions. The structures of the target compounds were characterized by IR,1H NMR and elemental analyses.2. The bioavailability parameters of the title compounds were computed by computer andrelated softwares. The calculated results of drug-likeness property indicated that most ofthe title compounds have good oral bioavailability.3. The reaction mechanism that generates the target compound, the impact of electronegativeand position of substituent on the reaction selectivity, the relationship between structure andactivity had been discussed.4. The newly synthesized target compounds were screened for their biological activities. Theassay results of inhibitory activity against Cdc25B phosphatase show that most ofacylthiosemicarbazide exhibit higher activity, and VII1, VII9, VII12, VII14and VII15exhibited higher activity (IC50=0.53,1.09,0.59,1.07,0.86) than Na3VO4(IC50=1.13).VII10、VIII2、VIII3and VIII4exhibited high activity against PTP1B. VII10and VII11exhibited weak scavenging activities against DPPH. Diacylhydrazine exhibited lackactivitiy against Cdc25B, PTP1B and DPPH.5. In conclusion, most of the target compounds show higher inhibitory activity againstCdc25B phosphatase and PTP1B. These activities make them attractive candidates forfurther assessment in anticancer, diabetes and obesity agents.