氨基甲酸酯衍生物的癌症化学预防活性。

Cancer chemopreventive activity of sulforamate derivatives.

作者信息

Moriarty Robert M, Naithani Rajesh, Kosmeder Jerome, Prakash Om

机构信息

4500, Department of Chemistry, SES Building, 845, W. Taylor Street, University of Illinois at Chicago, Chicago 60607, IL, USA.

出版信息

Eur J Med Chem. 2006 Jan;41(1):121-4. doi: 10.1016/j.ejmech.2005.10.002. Epub 2005 Nov 21.

DOI:10.1016/j.ejmech.2005.10.002

PMID:16300858

Abstract

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.

摘要

化学预防可定义为通过使用天然或合成物质对致癌过程进行的干预。诱导II相酶是化学预防的重要机制。在本研究中，我们合成了几种(+)(-) 4-甲基亚磺酰基-1-(S-甲基二硫代氨基甲酰基)-丁烷（亚磺酰胺）的衍生物，并评估了它们作为NAD(P)H醌氧化还原酶[醌还原酶(QR)]（一种II相酶）在培养的Hepa1c1c7小鼠肝癌细胞中的单功能诱导剂的有效性。与[(-)-1-异硫氰酸酯-4(R)-(甲基亚磺酰基)丁烷]（萝卜硫素）相比，一些衍生物的细胞毒性大大降低。然而，这些化合物的诱导潜力与萝卜硫素相当。基于这些结果，亚磺酰胺衍生物可被视为简单、廉价且易于获得的化学预防剂。