Cancer chemopreventive activity of sulforamate derivatives.
Chemoprevention can be defined as an intervention in the carcinogenic process by use of natural or synthetic substances. Induction of Phase II enzyme is an important mechanism of chemoprevention. In the present studies we have synthesized several derivatives of (+)(-) 4-methylsulfinyl-1-(S-methyldithiocarbamyl)-butane (sulforamate) and evaluated their effectiveness as monofunctional inducer of the NAD(P)H Quinone oxidoreductase [quinone reductase (QR)] a phase II enzyme in cultured Hepa1c1c7 murine hepatoma cells. The cytotoxicity of some of the derivatives was strongly reduced in comparison to [(-)-1-isothiocyanato-4(R)-(methylsulfinyl)butane] (sulforaphane). However, the induction potential of these compounds was comparable to sulforaphane. On the basis of these results sulforamate derivatives can be regarded as simple, inexpensive and readily available chemopreventive agents.
Moriarty
Robert M
RM
4500, Department of Chemistry, SES Building, 845, W. Taylor Street, University of Illinois at Chicago, Chicago 60607, IL, USA.
Naithani
Rajesh
R
Kosmeder
Jerome
J
Prakash
Om
O
D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D017879:Isothiocyanates; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D013454:Sulfoxides; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology*; D013861:Thiocyanates / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013859:Thiocarbamates; D013861:Thiocyanates; C103653:sulforamate; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C016766:sulforaphane