Hydrolytic pathway protects against ceramide-induced apoptosis in keratinocytes exposed to UVB.

Although ceramides (Cers) are key constituents of the epidermal permeability barrier, they also function as apoptogenic signals for UVB irradiation-induced apoptosis in epidermal keratinocytes. As epidermis is continuously exposed to UV irradiation, we hypothesized that Cer hydrolysis protects keratinocytes from UVB-induced apoptosis by attenuating Cer levels. Both low-dose UVB (L-UVB) (< 35 mJ cm(-2)) and high-dose UVB (H-UVB) (> or = 45 mJ cm(-2)) irradiation inhibited DNA synthesis in cultured human keratinocytes, but apoptosis occurred only after H-UVB.

New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.

The synthesis of new antitumor 6-substituted imidazothiazole guanylhydrazones is described. Moreover, a series of compounds with a different basic chain at the 5 position were prepared. Finally, the replacement of the thiazole ring in the imidazothiazole system was also considered.

Allylic structures in cancer drugs and body metabolites that control cell life and death.

This review presents data supporting the hypothesis that the anticancer activity of ceramide and many antineoplastic drugs is due to a 3-carbon allylic moiety (-C = C-C-) containing oxygen or nitrogen. The polar atom appears as an alcohol, ether, ester, amide, ketone, amine or imino group. Some drugs lack the allylic moiety, but metabolic oxidation or oxygenation in patients introduces the moiety.

Meta-analysis of anticancer drug structures--significance of their polar allylic moieties.

This meta-analysis examines a wide range of small molecule anticancer drugs to search for a structure common to all. Although they encompass a very wide range of structures, nearly all reveal the presence of an allylic O, N, or S atom. In some, the allylic oxygen is a carbonyl group, or an alcohol group, which can be substituted (ester, lactone, glycoside, ether) or replaced by an amino or imino nitrogen Some antineoplastic drugs do not exhibit this moiety but are converted in vivo to allylic derivatives.

Preventing the binding of pathogens to the host by controlling sphingolipid metabolism.

The binding of many pathogens and toxins to human cells can be inhibited by (1) depleting host cells of their surface glycosphingolipids; (2) coating the binding sites on pathogens (adhesins) with glycosphingolipid-like substances (decoys); (3) coating the host's glycosphingolipids with substances that compete with the pathogen for binding. Details of using these methods are described.