Selective and slow-binding inhibition of shikonin derivatives isolated from Lithospermum erythrorhizon on glycosyl hydrolase 33 and 34 sialidases.
Sialidases are enzymes that catalyze the hydrolysis of sialic acid residues from various glycoconjugates, which are widely found in a number of viral and microbial pathogens. In this study, we investigated the biological evaluation of isolated six shikonins (1-6) and three shikonofurans (7-9) from Lithospermum erythrorhizon. The nine isolated compounds 1-9 showed strong and selective inhibition of glycosyl hydrolase (GH) 33 and -34 sialidases activities. In GH33 bacterial-sialidase inhibition assay, the inhibitory activities against GH33 siadliase of all shikonofuran derivatives (7-9) were greater than shikonin derivatives (1-6). Shikonofuran E (8) exhibited the most potent inhibitory activity toward GH33 sialidases (IC(50)=0.24μM). Moreover, our detailed kinetic analysis of these species unveiled that they are all competitive and simple reversible slow-binding inhibitors. Otherwise, they showed different inhibitory capacities and kinetic modes to GH34 viral-sialidase activity. All the naphthoquinone derivatives (1-6) were of almost equal efficiency with IC(50) value of 40μM and shikonofurans (7-9) did not show the significant inhibitory effect to GH34 sialidase. Kinetic analyses indicated that naphthoquinones acted via a noncompetitive mechanism.
Infection Control Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea.
Ji Young
JY
Kim
Hyung Jae
HJ
Jeong
Ji-Young
JY
Park
Young Min
YM
Kim
Su-Jin
SJ
Park
Jung Keun
JK
Cho
Ki Hun
KH
Park
Young Bae
YB
Ryu
Woo Song
WS
Lee
D006026:Glycoside Hydrolases / Q000737:chemistry*; D006867:Hydrolases; D007700:Kinetics; D029684:Lithospermum / Q000737:chemistry*; D009285:Naphthoquinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009439:Neuraminidase / Q000737:chemistry*
D009285:Naphthoquinones; C016101:shikonin; D006867:Hydrolases; D006026:Glycoside Hydrolases; D009439:Neuraminidase