Pharmacophore modeling studies on known mmp-9 enzyme inhibitors to identify the important common features
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Date
2020
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Publisher
Ankara Üniversitesi
Abstract
Objective: In this study, pharmacophore models were generated to explain the structure–activity relationships
by using the known MMP-9 inhibitors.
Material and Method: Pharmacophore models were generated to explain the specification of the structure–
activity relationships of common pharmacophoric sites of the known MMP-9 inhibitors. For this study
Discovery Studio 3.5 software was used. A set of known MMP-9 inhibitors (NFH, Batimastat, Marimastat,
Prinomastat, CGS-27023A, and Ro32-3555) were used for common feature pharmacophore generation method.
Selected hypothesis included two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic
feature.
Result and Discussion: All of the tested inhibitors except CGS-27023A and Ro32-3555 fitted the selected
pharmacophore model perfectly. These two inhibitors did not fit the A2 feature. It can be concluded that A1,
D1, and H1 features at the given positions could be necessary for the activity. Additionally, we compared the
pharmacophore model with NFH and MMP-9 enzyme complex to identify the important interactions. At the
given positions of all of the pharmacophoric features, there is an interaction with the protein. This is also
supported our pharmacophore hypothesis. As a result, this pharmacophore model could be useful to design new
small molecule inhibitors of MMP-9 enzyme
Description
Keywords
Cancer, İnflammatory diseases, Pharmacophore modeling, Enflamatuar hastalıklar, Farmakofor modelleme, Kanser