Effects of 1-tetradecylperhydroazepine and 1-pentadecylpiperidine N-oxides on Ehrlich ascites mitochondria.
Non-aromatic amine oxides are widely known and used compounds. A great number of amine oxides occurring in nature, or prepared synthetically, are biologically active compounds (antimetabolites and chemotherapics, cancerostatic compounds, etc.). From seven series of newly synthesized amine oxides (63 compounds), 1-alkylperhydroazepine N-oxides (PHNO) and 1-alkylpiperadine N-oxides (PINO) have been chosen for further investigation. The effects of 8 derivatives of PHNO and 8 derivatives of PINO on state 3 and 4 respiration of Ehrlich ascites mitochondria (EAM) have been studied. Derivatives with longer side-chain significantly affected respiration of EAM according to the substrates used. To elucidate the mode of action, the most potent amine oxides from each series, 1-tetradecylperhydroazepine N-oxide (tPHNO) and 1-pentadecylpiperidine N-oxide (pPINO) have been chosen for further study. Both amine oxides stimulated state 4 respiration with glutamate-malate and succinate as substrates. The effect on state 3 respiration depended on the substrates used. Both tPHNO and pPINO were able to release respiration of EAM previously inhibited by oligomycin, both decreased the level of ATP in EAM. ATPase activity was significantly stimulated by both drugs only in higher concentrations. A possible mode of action of amine oxides on oxidative phosphorylation and the relationship between chemical structure are discussed.
Miko
M
M
Department of Microbiology, Biochemistry and Biology, Slovak Technical University, Bratislava, Slovakia.
Devinsky
F
F
D000251:Adenosine Triphosphatases / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000648:ultrastructure; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D015394:Molecular Structure; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001381:Azepines; D003497:Cyclic N-Oxides; D010880:Piperidines; C098562:1-pentadecylpiperidine N-oxide; C098561:1-tetradecylperhydroazepine N-oxide; D000251:Adenosine Triphosphatases