Synthesis and evaluation of cytotoxic activities of some 1,4-disubstituted thiosemicarbazides, 2,5-disubstituted-1,3,4-thiadiazoles and 1,2,4-triazole-5-thiones derived from benzilic acid hydrazide

Abstract

This study describes the synthesis of novel 1-(α,α-diphenyl-α-hydroxy)acetyl-4- substitutedthiosemicarbazide (2a-k), [5-(substitutedamino)-1,3,4-thiadiazole-2-yl](diphenyl) methanol (3a-b) and 3-[hydroxy(diphenyl)methyl]-4-(nonsusbtituted/substituted)-2,4-dihydro- 5H-1,2,4-triazole-5-thione derivatives (4a-c) and evaluation of their cytotoxic activities. In the course of the syntheses benzilic acid methyl ester was reacted with hydrazine hydrate in absolute ethanol to afford benzilic acid hydrazide (1). Reaction of 1 with appropriate alkyl/ arylisothiocyanates gave 1-(α,α-diphenyl-α-hydroxy)acetyl-4-substitutedthiosemicarbazide (2a-k). [5-(substitutedamino)-1,3,4-thiadiazole-2-yl](diphenyl)methanol derivatives (3a-b) were obtained by cyclization of 2a and 2c with concentrated sulphuric acid. On the other hand, 3-[hydroxy(diphenyl)methyl]-4-(nonsusbtituted/substituted)-2,4-dihydro-5H-1,2,4-triazole- 5-thione (4a-c) were obtained by cyclization of 2c, 2d and 2g with 2N NaOH. The structures of the new compounds were confirmed by the data obtained from elemental analysis, HPLC, UV, IR, 1H-NMR, 13C-NMR, HSQC and MS spectra. Compounds 2a, 2c-k, 3b and 4b were selected for cytotoxic screening by using HEK293 cell line of MTT assay. The highest inhibition were confirmed as 50.23% at 10 mg/ml for the compound 1-(α,α-diphenyl-α- hydroxy)acetyl-4-cyclohexylmethylthiosemicarbazide (2e).