Role of the naphthoquinone moiety in the biological activities of sakyomicin A.
The naphthoquinone moiety was proven to be essential to the biological activities of sakyomicin A using various naphthoquinone derivatives. Among the naphthoquinones tested, juglone (5-hydroxy-1,4-naphthoquinone) which resembles the partial structure of sakyomicin A was the most active in cytotoxicity against murine lymphosarcoma L5178Y cells, electron acceptor function in the oxidation of NADH by Clostridium kluyveri diaphorase or rat liver mitochondria and inhibition against avian myeloblastosis virus reverse transcriptase. The significantly lower cytotoxicity of sakyomicin A as compared with juglone was attributable to its poor membrane transport. The inhibition of reverse transcriptase activity may result from the interaction between a sulfhydryl group in the active center of the enzyme and quinone groups of the naphthoquinones and sakyomicin A.
Y
Y
Take
M
M
Sawada
H
H
Kunai
Y
Y
Inouye
S
S
Nakamura
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016227:Benzoquinones; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D009285:Naphthoquinones; D011809:Quinones; D018894:Reverse Transcriptase Inhibitors; D009243:NAD; C042536:sakyomicin A; D006861:Hydrogen Peroxide