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- Title
Computational studies on structural modifications for the inhibition of matrix metalloproteinase activities by luteolin.
- Authors
Zhang, Ji; Li, Hui; Zhou, Xia; Fan, Yi-Ran; Zhou, Zhi-Guang; Yao, Qi-Zheng
- Abstract
Many experimental studies have previously found that flavonoids including luteolin can inhibit the activities of matrix metalloproteinases (MMPs), but the related theoretical studies are rather lacking. In this paper, based on our recently obtained interaction mechanisms between luteolin and the catalytic zinc ion in MMPs (see J. Phys. Org. Chem.2012, 25, 1306), we perform PM6 quantum chemistry calculations together with modeling of ligand−water exchange reactions to investigate the relevant structural modifications for the inhibition of MMP activities by luteolin. The calculations indicate that among the possible modified positions of A, B, and C rings of the luteolin molecule, 5, 7, 2′, 3′, and 4′ should be the five suitable modified positions, and the several usual substituent groups that have stronger electron-donating abilities should be the suitable substituent groups. We further find that with the increasing number of these substituent groups, the biological activities for the modified luteolin molecules on MMP inhibition can be obviously improved. Our calculated results are in agreement with previous relevant experimental results. This paper gives a new approach for designing the new MMP inhibitors having higher biological activities by carrying out the structural modifications of the luteolin molecule.
- Subjects
MATRIX metalloproteinases; LUTEOLIN; EXCHANGE reactions; ZINC ions; QUANTUM chemistry; FLAVONOIDS
- Publication
Canadian Journal of Chemistry, 2013, Vol 91, Issue 10, p1009
- ISSN
0008-4042
- Publication type
Article
- DOI
10.1139/cjc-2013-0140