Comparison of the effects on mitochondrial function of a series of 2-methyl substituted 1,4-naphthoquinones to their 6-methyl counterparts.
Seven derivatives of 2-methyl-1,4-naphthoquinone were compared to an equivalent series of 6-methyl-1,4-naphthoquinone derivatives for their abilities to interact with mitochondrial membranes and enzyme systems. The substituents on the methyl groups included various electron-withdrawing and -donating groups. The 6-methyl quinones were, in general, more potent inhibitors of NADH-oxidase and succinoxidase, depleted sulfhydryl groups more completely, produced greater rates of cyanide (CN-)-insensitive respiration (respiratory bursts), and induced more severe large-amplitude mitochondrial swelling than the analogous 2-methyl quinones. The NADH-oxidase system was more sensitive than succinoxidase to inhibition by both series, suggesting that Complex I is the primary site of inhibition by these quinones.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002417:Cattle; D003486:Cyanides / Q000494:pharmacology; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009285:Naphthoquinones / Q000494:pharmacology* / Q000633:toxicity; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003486:Cyanides; D009097:Multienzyme Complexes; D009285:Naphthoquinones; D010088:Oxidoreductases; C022691:succinate oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases