Synthesis, antimycobacterial and antitumor activities of new (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl N,N-disubstituted dithiocarbamate/O-alkyldithiocarbonate derivatives

Abstract

Reaction of 2-chloromethylsaccharin with substituted potassium dithiocarbamates and substituted potassium dithiocarbonates furnished (1, 1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl NN-disubstituted dithiocarbamates (4-15) and (1, 1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyI O-alkyldithiocarbonates (16-20). The new derivatives were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Compounds 4-13, 15, and 16-20 described herein showed moderate to good inhibitory activity. In particular, seven analogs 4, 5, 6, 13, and 7, 8, and 12 exhibited excellent MIC values of 1.56 and 0.78 mu g/mL, respectively. Compounds 4, 5, 10, 12, 13, and 16 were selected and screened for antitumor activity. Among the tested compounds, 4 and 5 were found to be cytotoxic, especially against leukemia cell lines CCRF-CEM, HL-60(TB), RPMI-8226, and SR with log(10)GI(50) values lower than -6.69, and against non-small cell lung cancer NCI-H522 cell line with log(10)GI(50) values lower than -6.31. Compound 10 was cytotoxic against leukemia cell line HL-60(TB), whereas 16 displayed favorable cytotoxicity against ovarian cancer cell line OVCAR-3 with log(10)GI(50) values of -6.31 and -7.45, respectively. (c) 2006 Elsevier Ltd. All rights reserved.