Evaluation of Mannich bases and related compounds as inhibitors of mitochondrial function in yeast and inhibition of blood platelet aggregation, blood clotting, and in vitro metabolism of 5-dimethylamino-1-phenyl-1-penten-3-one hydrochloride.
Dimethylamino-1-phenyl-1-penten-3-one hydrochloride (Ia) and 32 analogs were tested for inhibition of respiratory-dependent growth in Saccharomyces cerevisiae. Thirteen of the 33 compounds tested appeared to affect mitochondrial function, since the inhibition of respiratory-dependent growth was statistically greater than the inhibition of growth on fermentable energy sources. Inhibition of mitochondrial function in yeast and growth inhibition of an in vitro culture of human epidermoid carcinoma (KB) were positively correlated since 83% of the compounds tested either had mitochondrial-inhibiting properties and significant activity in the KB test or were inactive in both tests. Similarly, 78% of compounds tested showed murine toxicity and mitochondrial inhibition or had no effect on murine toxicity and yeast mitochondrial function. Injection of Ia into rats resulted in the appearance of blood in the urine and feces. Compound Ia inhibited adenosine diphosphate and collagen-induced aggregation of rat platelets but had no effect on blood clotting. TLC, following incubation of Ia with a rat liver extract, showed that the structure of Ia was not enzymatically modified and indicated activity per se on platelet aggregation and mitochondrial function.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D010422:Pentanones / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000648:ultrastructure*
D000970:Antineoplastic Agents; D007659:Ketones; D010422:Pentanones; C012294:5-dimethylamino-1-phenyl-1-penten-3-one; D000244:Adenosine Diphosphate; D003094:Collagen