Güzel Ozlen, Salman Aydin
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazit, Istanbul, Turkey.
Bioorg Med Chem. 2006 Dec 1;14(23):7804-15. doi: 10.1016/j.bmc.2006.07.065. Epub 2006 Aug 22.
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.
2-氯甲基糖精与取代的二硫代氨基甲酸钾和取代的二硫代碳酸钾反应，得到(1,1-二氧化-3-氧代-1,2-苯并异噻唑-2(3H)-基)甲基N,N-二取代二硫代氨基甲酸盐(4-15)和(1,1-二氧化-3-氧代-1,2-苯并异噻唑-2(3H)-基)甲基O-烷基二硫代碳酸盐(16-20)。对这些新衍生物针对结核分枝杆菌H37Rv进行了体外抗分枝杆菌活性评估。本文所述的化合物4-13、15以及16-20显示出中等至良好的抑制活性。特别地，七个类似物4、5、6、13以及7、8和12分别表现出优异的最低抑菌浓度值，为1.56和0.78μg/mL。选择化合物4、5、10、12、13和16并筛选其抗肿瘤活性。在所测试的化合物中，发现4和5具有细胞毒性，尤其是对白血病细胞系CCRF-CEM、HL-60(TB)、RPMI-8226和SR，其log10GI50值低于-6.69，并且对非小细胞肺癌NCI-H522细胞系，其log10GI50值低于-6.31。化合物10对白血病细胞系HL-60(TB)具有细胞毒性，而16对卵巢癌细胞系OVCAR-3显示出良好的细胞毒性，其log10GI50值分别为-6.31和-7.45。
