ABSTRACT
Markedly inhibitory effects of Ca(2+) on the growth of human tumor cells were attained through the induction of apoptosis in vitro. On the other hand, a good correlation between the growth inhibition effects of Ca(2+) and the amounts of phosphatidylserines (PS) in the cell membranes (plasma membranes) was obtained. Furthermore, the decrease of membrane fluidity and the localization of lipid microdomains "lipid rafts" in the cell membranes were observed in the presence of Ca(2+). The findings in this study suggest that Ca(2+) could induce apoptosis toward tumor cells through the localization of lipid rafts in plasma membranes by the specific interactions between extracellular Ca(2+) and PS.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Calcium/pharmacology , Lipid Metabolism/drug effects , Neoplasms/metabolism , Phosphatidylserines/metabolism , Anions/metabolism , Antineoplastic Agents/metabolism , Antineoplastic Agents/therapeutic use , Calcium/metabolism , Calcium/therapeutic use , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/physiology , Humans , Membrane Fluidity/drug effects , Neoplasms/drug therapy , Trace Elements/metabolism , Trace Elements/pharmacology , Trace Elements/therapeutic useABSTRACT
A series of 2-anilinopyrimidines was prepared and their fungicidal activities against Botrytis cinerea Pers were examined. The activity fell sharply with any substitution on the anilinobenzene ring. Substituents at the 5-position of the pyrimidine ring greatly reduced the activity. Substituents such as chloro, methoxy, methylamino, methyl or 1-propynyl were well tolerated at the 4- and 6-positions of the pyrimidine ring. Among these substituents, the combination of methyl and 1-propynyl groups was the most favourable. 2-Anilino-4-methyl-6-(1-propynyl)pyrimidine (KIF-3535), which showed excellent activity and no significant phytotoxicity, was finally selected for development and has been given the common name mepanipyrim.
