Synthesis of esters of coenzyme PQQ and IPQ, and stimulation of nerve growth factor production.
Esters of pyrroloquinoline quinone (PQQ), a cofactor of microbial quinoprotein enzyme, and imidazopyrroloquinoline (IPQ, from PQQ and glycine) were synthesized, and their chemical stability, toxicity to L-M cells and nerve growth factor (NGF) inducing activity in L-M cells were studied. PQQ esters were found to be potent enhancers of NGF production, but IPQ esters had only marginal effects on NGF production. The monoester of PQQ with a methoxycarbonyl group at C-2 of PQQ is a most effective compound because of its NGF inducing activity, limited toxicity, safety and chemical stability. These results suggest that PQQ-2-esters could be developed as a curative or preventive drug for retrograde neural diseases in the central and perpheral nervous system.
Urakami
T
T
Biochemicals Division, Mitsubishi Gas Chemical Co., Tokyo, Japan.
Tanaka
A
A
Yamaguchi
K
K
Tsuji
T
T
Niki
E
E
D000818:Animals; D002460:Cell Line; D003067:Coenzymes / Q000138:chemical synthesis*; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis*; D006868:Hydrolysis; D051379:Mice; D015394:Molecular Structure; D009414:Nerve Growth Factors / Q000096:biosynthesis; D045542:PQQ Cofactor; D011758:Pyrroles / Q000138:chemical synthesis*; D011804:Quinolines; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
C104140:7,10-dihydro-7-oxoimidazo(4,5,1-ij)pyrrolo(2,3-f)quinoline-1,3,9-tricarboxylic acid; D003067:Coenzymes; D004952:Esters; D009414:Nerve Growth Factors; D011758:Pyrroles; D011804:Quinolines; D015363:Quinolones; D045542:PQQ Cofactor