Preliminary Study On Synthesis And Antifungal Activities Of Thiosemicarbazone Derivatives Of N-Benzylindoles

Indoles and thiosemicarbazones have attracted much attention due to their antimicrobial,antiviral and antitumor activities.Previously,indoles and thiosemicarbazones were found to display the antifungal activities in our team.Therefore,in this paper,a series of thiosemicarbazone derivatives of N-benzylindoles were designed and synthesized,and their antifungal activities were tested.The main results were as follows:1.By using indole（I1）,5-cyanoindole（I2）,6-methylindole（I3）and 7-methylindole（I4）as lead compounds,intermediates Ⅱ1-4 and Ⅲ1-23 were firstly synthesized.Then the target compounds Ⅳ1-Ⅳ27 were obtained by condensation of Ⅱ1-4 and Ⅲ1-23 with the amino thiourea.All compounds were characterized by¹H NMR,and the melting points.Furthermore the configuration of compounds Ⅳ15 and Ⅳ16 was determined by X-Ray single crystal diffraction.2.The antifungal activities of target compounds Ⅳ1-Ⅳ27 were tested against six phytopathogenic fungi,such as Curvularia lunata,Valsa mali,Alternaria alternate,Fusarium graminearum,Botrytis cinerea and Fusarium solani,at 100μg/m L after 96 h treatment.Compounds Ⅳ5-Ⅳ9,Ⅳ18 and Ⅳ22-Ⅳ27 showed significant antifungal activity on V.mali.3.Compared with those of the indole（I1）,compounds Ⅳ1 and Ⅳ5-Ⅳ9 showed higher antifungal activities.Among them,compound Ⅳ7 displayed the most significant antifungal activity against V.mali,and its EC₅₀value was 0.66μg/m L,which was 77.2-fold compared with that of indole(EC₅₀=50.98μg/m L).The antifungal activities of compound Ⅳ5 against C.lunata and A.alternate was higher than those of the positive control carbendazim.4.QSAR showed that,introducing an electron-withdrawing group（R¹=CN）into the indole ring could decrease the antifungal activities;introduction of some（substituted）benzyl on the N-1 position of Ⅳ1 and Ⅳ4 led to more potent compounds（such as Ⅳ6,Ⅳ9,Ⅳ22and Ⅳ23）;when R¹=H,the antifungal activities of all target compounds were higher than those of indole.In short,27 thiosemicarbazone derivatives of N-benzylindoles（Ⅳ1-Ⅳ27）were synthesized,and their antifungal activities were studied against six phytopathogenic fungi.Compound Ⅳ5 showed the potent antifungal activities.It was found that introduction of the thiosemicarbazone fragment on the C-3 position and（substituted）benzyl on the N-1 position of indole can enhance the antifungal activities of the corresponding compounds.It will pave the way for further development of indole derivatives as antifungal agents.