Tyrosinase inhibitory polyphenols from roots of Morus lhou.
Twelve polyphenols (1-12) possessing tyrosinase inhibitory properties were isolated from the methanol (95%) extract of Morus lhou. The isolated compounds consisted of four flavanones (1-4), four flavones (5-8), and four phenylbenzofuranes (9-12). Moracin derivative 12 proved to be new a compound which was fully characterized. Compounds 1-12 were evaluated for both monophenolase and diphenolase (the two steps catalyzed by tyrosinase) inhibition to identify the structural characteristics required for mushroom tyrosinase inhibition. We observed that all parent compounds (1, 5, and 9) possessing an unsubstituted resorcinol group were highly effective inhibitors of monophenolase activity (IC(50) values of 1.3, 1.2, and 7.4 microM). The potency of the inhibitors diminished with alkyl substitution on either the aromatic ring or the hydroxyl functions. Interestingly, flavone 5 was shown to possess only monophenolase inhibitory activity, but flavanone 1 and phenylbenzofuran 9 inhibited diphenolase as well as monophenolase significantly. The inhibitory mode of these species was also dependent upon the skeleton: phenylbenzofuran 9 manifested a simple competitive inhibition mode for monophenolase and diphenolase; on the other hand flavanone 1 (monophenolase, k(3) = 0.1966 min(-1) microM(-1), k(4) = 0.0082 min(-1), and K(i)(app) = 0.0468 microM; diphenolase, k(3) = 0.0014 min(-1) microM(-1), k(4) = 0.0013 min(-1), and K(i)(app) = 0.8996 microM) and flavone 5 both showed time-dependent inhibition against monophenolase. Compound 1 operated according to the simple reversible slow binding model whereas compound 5 operated under the enzyme isomerization model.
Jeong
Seong Hun
SH
Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Korea.
Ryu
Young Bae
YB
Curtis-Long
Marcus J
MJ
Ryu
Hyung Won
HW
Baek
Yoon Su
YS
Kang
Jae Eun
JE
Lee
Woo Song
WS
Park
Ki Hun
KH
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D031625:Morus / Q000737:chemistry* / Q000201:enzymology; D010636:Phenols / Q000302:isolation & purification* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*; D059808:Polyphenols
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D014442:Monophenol Monooxygenase