title: QSAR and kinetics of the inhibition of benzaldehyde derivatives against Sacrophaga neobelliaria phenoloxidase.
abstract: A group of 18 benzaldehyde derivatives was characterized as a family of mixed type inhibitors on the oxidation of l-3, 4-dihydroxyphenylalanine (l-DOPA) catalyzed by Sacrophaga neobelliaria phenoloxidase (PO), presumably by forming a Schiff base with a primary amino group of the enzyme. Inhibition constants and IC(50) were determined. Cuminaldehyde was the most active inhibitor with an IC(50) of 0.0067 mM. Vanillin was the least active inhibitor with an IC(50) of 38 mM. Four physicochemical descriptors were identified by stepwise multiple regressions as significant predictors on the inhibition activity, which were further rotated by principle component analysis yielding two significant principle properties. It was shown that hydrophobicity of the substituent at the para position of the aldehyde group played major role on inhibition activity: one unit increase in Hansch-Fujita pi value of the substituent led to about 4.5 [95% confidence interval is (7.9, 2.6)] fold increase on IC(50). Electron-donating effect of the substituent at the para position of the aldehyde group was less important than hydrophobicity. Hydroxyl group at the ortho position of the aldehyde group contributed to higher inhibition activity, presumably by forming a quasi-six-membered ring with the unshared pair of electrons on the nitrogen atom of the amino group through intramolecular hydrogen bonding.
authors.affiliation: Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Isao
authors.initials: I
authors.lastname: Kubo
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D016000:Cluster Analysis; D004175:Diptera / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D016014:Linear Models; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001547:Benzaldehydes; D007980:Levodopa; D014442:Monophenol Monooxygenase; C032175:benzaldehyde