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

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)methylidenebenzohydrazide (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-ylbenzamide (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 Daltonrsquo;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-ylbenzamide (4c), N-5-methyl-2-(4-nitrophenyl)-4-oxo-1,3-thiazolidin-3-ylbenzamide (4g) and N-2-(2,3- dichlorophenyl)-5-methyl-4-oxo-1,3-thiazolidin-3-ylbenzamide (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 mu;g/ml.