Study On Synthesis And Anticancer Activity Of Chiral Thiourea Containing Dipeptide And Phosphonate Moieties

Objective: To investigate the synthesis and anticancer activity of chiral thiourea compounds containing dipeptide and phosphonate moieties. Methods: In search of more effective anticancer agents, a splicing method was involved, by introducing active aminophosphonate group, fluorine atom group or chiral dipeptide amine into thiourea compounds with chiral α-amino acid, substituted benzylamine, ammonia, triethylamine, carbon disulfide, phosphorus oxychloride, substituted benzaldehyde, p-toluenesulfonic acid and dialkyl phosphite as the basic raw materials. And Twenty four novel compounds have been synthesized via four reaction steps. The cytotoxic activities of some of the compounds on A-549 in vitro were evaluated by using an 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl tetrazolium bromide（MTT） method with DMSO as a reference. Results:（1）24 novel chiral thiourea compounds containing dipeptide and phosphonate moieties were prepared via the series reactions of benzaldehyde, ammonia and dialkyl phosphite as the basic raw materials.They were reported for the first time. The structures of the title compounds were confirmed by IR, ¹H NMR, ¹³ C NMR, ¹⁹ F NMR, ³¹P NMR and HRMS.（2）Preliminary results in bioactivity tests indicated that some title compounds exhibited better activity against A-549, compounds showed more potent activities against A-549 with IC₅0 values of them ranged from 20.2 to 172.3 μmol/L. Conclusion: We designed and synthesized 24 novel chiral thiourea compounds containing dipeptide and phosphonate moieties according to the principle of combination of bioactive substructure. The compound O, O’-diisopropyl（3-（4-fluorobenzylamino-L- Proline-L- Phenylalanine）- α-thioureido）（phenyl） methylphosphonate showed more potent activities against A-549 with IC₅0 values of 20.2 μmol/L.