2006
DOI: 10.1124/mol.106.023119
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Abstract: In this work, we present a comparative case study of "ortho-" and "meta-nitrated" catecholic inhibitors of catechol-O-methyltransferase (COMT), with regard to their interaction with the catalytic site of the enzyme and the in vitro regioselective formation of their mono-O-methyl ether metabolites. In particular, the effects of altering the attachment position of the inhibitors' side-chain substituent, within the classic nitrocatechol pharmacophore, were investigated. For this purpose, we compared two simple re… Show more

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Cited by 49 publications
(50 citation statements)
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“…21 It should be noted that the crystal structure of a tolcapone derivative in the COMT enzyme shows that the nitro-substituent undergoes polar contact with a charged lysine side chains along with the catechol moiety. 32 This further confirms that a 4-susbtituted-3-nitrobenzene-1,2-diol (nitrocatechol) is a suitable pharmacophore to design small molecules as tau aggregation inhibitors.…”
Section: ■ Results and Discussionsupporting
confidence: 59%
“…21 It should be noted that the crystal structure of a tolcapone derivative in the COMT enzyme shows that the nitro-substituent undergoes polar contact with a charged lysine side chains along with the catechol moiety. 32 This further confirms that a 4-susbtituted-3-nitrobenzene-1,2-diol (nitrocatechol) is a suitable pharmacophore to design small molecules as tau aggregation inhibitors.…”
Section: ■ Results and Discussionsupporting
confidence: 59%
“…In contrast, the docking studies indicate that the orientation leading to 3Ј-O-methylation is energetically favorable. This conforms to the described binding mode of catecholic substrates to COMT (Palma et al, 2006;Bai et al, 2007) and our results in vitro, which show that 3Ј-O-methylation of catechins is clearly the major pathway. Therefore, we postulate that procyanidins may also be predominantly 3Ј-O-methylated by COMT.…”
Section: Methylation Of Catechins and Procyanidins In Vitrosupporting
confidence: 54%
“…We performed atomic scale molecular dynamics (MD) simulations using the five crystal structures for COMT [4][5][6][7] obtained from the PDB database [20]. One crystal structure each was obtained from structures 1VID, 1H1D, and 1JR4.…”
Section: Methodsmentioning
confidence: 99%
“…The third stucture is due to Bonifacio et al [6] who obtained a crystal structure for COMT with Mg 2þ ions, ADOMET, and the inhibitor BIA 3-335 (BIA) (PDB database structure identification 1H1D). Finally, and most recently, Palma et al [7] successfully crystallized COMT with Mg 2þ ions, ADOMET, and BIA 8-176 (BIE) (PDB structure identification 2CL5). BIA 3-335 and BIA 8-176 are both comprised of a DNC core structure with two different added tails.…”
Section: Introductionmentioning
confidence: 99%
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