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.
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 N,N-disubstituted dithiocarbamates (4-15) and (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl 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 microg/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 log10GI50 values lower than -6.69, and against non-small cell lung cancer NCI-H522 cell line with log10GI50 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 log10GI50 values of -6.31 and -7.45, respectively.
Güzel
Ozlen
O
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazit, Istanbul, Turkey. ozlen_guzel@yahoo.com
Salman
Aydin
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002254:Carbonates / Q000138:chemical synthesis / Q000494:pharmacology; D002264:Carboxylic Acids; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012439:Saccharin / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002254:Carbonates; D002264:Carboxylic Acids; D013844:Thiazoles; D013859:Thiocarbamates; D012439:Saccharin