According to active groups combination principle, a series of novel imine and imide derivatives bearing 1,2,4-triazole moiety was designed and synthesized. The key intermediate 3-substituted phenyl-4-amino-1,2,4-triazole-5-thiones was synthesized by esterification, hydrazinolysis, salt and cyclization reactions, and then was condensed with aromatic aldehydes and isobenzofuran-1,3-dione to obtain imine and imide derivatives, which were subjected to the thioetherification with suitable halides(RX) to produce the corresponding 24 novel imine and imide derivatives bearing 1,2,4-triazole moiety. The structures of target compounds were fully characterized by 1H NMR, IR, mass spectroscopy and elemental analysis. The preliminary bioassay results showed that most of the compounds possessed certain fungicidal activities. At the concentration of 150 mg/L, the inhibition rates of compounds 9a, 9d and 9e against Rhizoctonia solani were very similar with the commercial fungicide Flusilazole. Meanwhile, the preliminary structure-activity relationships(SAR) were discussed in order to investigate the essential structures required for their bioactivities. In addition, their in vitro antitumor activities were evaluated against three cancer cell lines[human alveolar epithelial cells(A549), human breast cancer cells(MD-MBA-231) and human prostate cancer cells(PC-3M)] by the methyl thiazolyl tetrazolium(MTT) chromatometry method with Fluorouracil as a positive contrast drug. The bioassay data indicated that compounds 7c, 7f and 9k showed similar antiproliferation with Fluorouracil against A549 cell lines with IC50 values of 38.3, 44.6 and 36.7 μmol/L, respectively. Most interestingly, compound 9k also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC50 values of 147.5 and 60.7 μmol/L, respectively.
