Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltipraz.

Oltipraz and related dithiolethiones constitute an important class of chemopreventive agents that enhance the expression of carcinogen detoxication and antioxidant genes. Dose-response studies were undertaken to characterize the cancer chemopreventive activities of several dithiolethiones that are at least as active as oltipraz as inducers. Inhibition of formation of pre-neoplastic lesions and formation of DNA adducts in livers of rats exposed to aflatoxin B1 (AFB1) was monitored.

Induction of NAD(P)H quinone: oxidoreductase1 inhibits carcinogen-induced aberrant crypt foci in colons of Sprague-Dawley rats.

Phase II detoxifying enzymes like NAD(P)H (quinone acceptor)oxidoreductase1 (NQO1), glutathione S-transferases (GST), and UDP-glucuronyltransferases (UGT) may play an important role in preventing carcinogen-induced cancers. Inducers of these enzymes have been shown to inhibit carcinogen-induced colon tumors in rat and mouse models. However, it has not been clearly demonstrated that NQO1 contributes to this effect.

Thionation with the reagent combination of phosphorus pentasulfide and hexamethyldisiloxane.

The combination of P4S10 and hexamethyldisiloxane efficiently converts esters, lactones, amides, lactams, and ketones to their corresponding thiono derivatives. In the presence of elemental sulfur, 3-oxoesters are converted to dithiolethiones by this reagent. Yields are comparable to or superior to those obtained with Lawesson's reagent.