Synthesis, Characterization and Antiproliferative Activity of Some Novel N-[2-(substitutedphenyl)-5-methyl-4-oxo-1,3-thiazolidin-3-yl]benzamides

摘要

1,3-Thiazolidin-4-one analogues are important because of its versatile biological actions. In the present study, benzohydrazide (1) on condensation with different aromatic aldehydes (2a-g) in presence of catalytic amount of concentrated hydrochloric acid in absolute ethanol yield N'-[(E)- (substitutedphenyl)methylidene]benzohydrazide (3a-g), which on cyclisation with 2- sulfanylpropanoic acid in dry 1,4-dioxane in presence of anhydrous zinc chloride afford the corresponding N-[2-(substitutedphenyl)-5-methyl-4-oxo-1,3-thiazolidin-3-yl]benzamide (4a-g). The structure of the newly synthesized compounds (3a-g) and (4a-g) were confirmed by IR and 1H NMR spectral data. All the newly synthesized 1,3-thiazolidin-4-one analogues (4a-g) at various concentrations (10, 20, 50, 100 and 200 mcg/ml) have been evaluated for in vitro cytotoxicity against Dalton’s ascites lymphoma (DAL) cancer cell line by trypan blue exclusion method. Compound N-[2-(2,4-dichlorophenyl)-5-methyl-4-oxo-1,3-thiazolidin-3-yl]benzamide (4c), N-[5-methyl-2-(4-nitrophenyl)-4-oxo-1,3-thiazolidin-3-yl]benzamide (4g) and N-[2-(2,3- dichlorophenyl)-5-methyl-4-oxo-1,3-thiazolidin-3-yl]benzamide (4b) inhibited 100%, 86% and 85% DAL tumor cells at 100 mcg/ml concentration, whereas standard drug doxorubicin exhibit 100% DAL inhibition at a concentration of 100 mcg/ml. From the above study, compounds 4b, 4c and 4g which showed better results ( 50% inhibition) at lowest concentration were selected for their in vitro antiproliferative activity against L929 lung fibroblast cell line by using MTT 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method. In the antiproliferative assay, among three compounds screened, compound 4c emerged as more potent inhibitor (30.35% at 10 mcg/ml conc) of L929 with an IC50 of 16.3 μg/ml.