Synthesis And Biological Activity Of 3-heterocyclic Thioindole Derivatives

Tumor is an important disease that endangers human's health,and chemotherapy is one of the most effective methods for tumor treatment.Heterocyclic compounds containing one or more heterocyclic atoms bind to biological targets effectively through the characteristics of hydrogen bond donors and receptors.In this study,a series of novel indole derivatives containing a disulfanyl azole heterocyclic was designed,synthesized and fully characterized by ¹H NMR,¹³C NMR and HRMS.Previous studies have found that the 3-position heterocyclic indole derivative has a good structure-activity relationship with EGFR,so the proliferative activity of target compounds against Hep G2,K562,A549 and CP-3 cancer cell lines was evaluated by the MTT method in vitro using Gefitinib as a positive control.At the same time,rat kidney cells NRK-52E were used to evaluate the toxicity of the drug to normal cells.The results showed that compounds 9a,9c,9d,10a,and 10b had better inhibitory effects on Hep G2.Further,the corresponding IC₅₀ values of them were 29.8±1.60?M,20.36±10.48?M,17.63±8.20?M,18.31±1.53?M,and 23.57±1.61?M,which were superior to the inhibitory effects of the control drug gefitinib(31.48±5.23?M).Three plant bacterias(Xanthomonas oryzae pv.Oryzae,Xoo;Pseudomonassyringae pv.actinidae,Psa;Xanthomonas axonopodis pv.Citri,Xac)were selected as test strains.The turbidity method was used to evaluate the inhibition rate of 14 target compounds against three plant pathogenic bacterias,and leaf cumazole(BMT)and copper thiazole(DTC),which have broad-spectrum inhibitory activity against plant pathogens,were used as positive control drugs.The results showed that the target compounds had strong inhibitory activity against three plant pathogenic bacterias,exceeding the positive control drug.Finally,the structure-activity relationship revealed that the activities of compounds were mainly related to the type of azoles heterocyclic and lipophilic side chains.