Synthesis, Characterization And Biological Activities Of Novel2,5-Disubstituted-1,3,4-thiadiazole Derivatives

1. Based on many literatures, nineteenth novel2,5-disubstituted-1,3,4-thiadiazole containingdiaryl ethers moiety (5a~5s) and sixteen novel2,5-disubstituted-1,3,4-thiadiazolecontaining benzisoselenazolone (7a~7i) were synthesized. The structures of the targetcompounds were characterized by IR,1H NMR and elemental analysis.2. The bioavailability parameters of the title compounds were calculated by computer andrelated softwares. The calculated results of drug-likeness property indicated that most ofthe title compounds have good oral bioavailability.3. The newly synthesized target compounds were screened for their Cdc25B，PTP1B，antitumor and antioxidant activities.①．Most compounds5and7have inhibitory activity against Cdc25B, the inhibitoryactivity against Cdc25B of compound5m and5f are equal to positive control Na3VO4(IC50=0.93M) with IC50value1.18and1.24M, respectively. Compound7n and7lhave higher inhibitory activity against Cdc25B than positive control Na3VO4(IC50=1.49M).②．Most compounds5have inhibitory activity against PTP1B, compound5n have thebest inhibitory activity against PTP1B (IC50=1.88M). All the compound7showinhibitory activity against PTP1B (IC50=0.32~2.05M)，and part of the compound’sactivity is than positive control Oleanolic acid (IC50=0.87M).③．Compound5r shows the best inhibitory activity against A-549with IC50=1.947g/mLwhich is equal to positive control5-FU (IC50=1.84g/mL).5e and5h have moderateactivity with inhibiton of44.91%and46.86%, respectively.5b and5h have weak activityagaist HCT-8with inhibiton of24.42%and21.37%, respectively. Compound5a~5sshow no inhibitory activity against Bel-7402. Compound7k has inhibitory activity againstHCT-8(IC50=5.475g/mL), and compound7i shows moderate activity against A-549with inhibition of41.37%, while compound7b,7f,7j~7l and7p have weak activity withinhibition19.18~36.11%. Compound7f and7k show weak activity aganst Bel-7402withinhibition19.90%and14.40%, respectively.④．Compound7a~7p show moderate hydroxyl radical scavenging activity, whichcompound7o has the best activity with inhibition of48.24%. Compound7e and7p show moderate superoxide anion radical scavenging activity with inhibition of39.09%and42.51%, respectively. All compound7show no DPPH·scavenging activity.4．The screened target compounds have potential value in the anti-cancer, anti-diabetes andobesity, antioxidant areas. This reaserch provides a strong basis for the findings of newanti-cancer, anti-diabetes and obesity, the development of antioxidant drugs.