| ObJective:In order to study the synthesis and antitumor and antibacterial activity of oligopeptide chiral thiourea compounds.Methods:Based on previous work,a series of noval oligopeptide chiral thioureas have been synthesized by using C-to-N synthesis strategy and coupling reagent O’-benzotriazole-N,N,N’,N’-tetramethylurea（HBTU）.Substituted benzylamines,amino acids and dialkyl phosphonate were employed as the starting materials,and the trifluoromethyl,nitrogen-containing heterocycles,etc.were introduced.The cytotoxicity of the target compounds against two tumor cells PC-3 and A-549 were tested in vitro by using MTT assay and DMSO as a reference.Two-fold dilution method was used to detect the minimum inhibitory concentrations（MIC）of target compounds against E.cloacae,S.aureus,and P.vulgaris.Results:（1）26 novel oligopeptide chiral thioureas were synthesized by subjected to reactions such as condensation,phosphonate esterification,hydrolysis,and nucleophilic substitution.The structures of the target compounds were confirmed and characterized by IR,(1H,13C,31P,19F)NMR and UPLC-ESI-MS/MS.（2）The antitumor activity results indicate thatⅢ22 had the best inhibitory activity against PC-3 cells（IC50:17.1μmol/L）;Ⅲ23 had the best inhibitory activity against A-549 cells(IC50:15.6μmol/L)and was comparable to the control agent cisplatin（IC50:14.8μmol/L）.（3）The results of the antibacterial test showed that some compounds have potential inhibitory effects on the Gram-negative bacteria P.vulgaris.In particular,the minimum inhibitory concentration（MIC）values of compoundsⅢ4,Ⅲ12 andⅢ16 against P.vulgaris were all 1.56 mg·mL-1.Conclusion:The oligopeptide chiral thiourea compounds were synthesized by the principle of reactive group splicing.The compoundⅢ233 has potential anti-tumor activity and deserves further study with previous work.The compoundsⅢ4,Ⅲ12,andⅢ16 have potential inhibitory effects on P.vulgaris,providing the basis for studies on the antibacterial of these compounds. |
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