Synthesis, Characterization And Biological Activities Of Some Novel1,2,4-Triazine Derivatives Containing Benzimidazole Moiety

1. Forty five novel3,6-disubstituted-1,2,4-triazines (V1~45) containing benzimidazole moietywere synthesized by o-phenylenediamine and aryloxyacetic acids 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, containing percentage of absorption (%ABS), molecular volume(Volume), topological polar surface area (TPSA), number of rotatable bonds (NROTB),number of hydrogen bond donors (HBA), number of hydrogen bond acceptors (HBD),octanol/water partition coefficient (LogP), molecular weight (MW). The calculated resultsof drug-likeness property indicated that the title compounds have good oralbioavailability.3. The newly synthesized target compounds (V1~45) were screened for their biologicalactivities. The assay results of inhibitory activity against Cdc25B phosphatase show thatmost of them exhibit higher activity at20μg/mL and the inhibitory rate are in the range of50%~98.5%. The results suggest that the target compounds have good anticancer activity.The assay results of inhibitory activity against PTP1B exhibit that twenty title compoundsshow higher activity at20μg/mL and the inhibitory rate are in the range of50%~95.4%.The results showed that the target compounds have good antidiabetic and obese activity.The results of in-vitro antitumor assay indicate that several compounds exhibit weakactivity to liver cancer (Bel-7402) and intestines cancer (HCT-8) at10μg/mL and theinhibitory rate are in the range of9.4~9.6%and17.4~31.2%respectively, but no activityto lung cancer (A-549). The assay results of inhibitory activity against protein tyrosinekinase (PTK) show that several target compounds have weak inhibitory activity at10μg/mL and the inhibitory rate are in the range of20.46~25.76%.4. In conclusion, the assay results of biological activity show that most of the targetcompounds show higher inhibitory activity against Cdc25B phosphatase and PTP1B. Theseactivities make them attractive candidates for further assessment in anticancer, diabetes andobesity agents.