title: A quantitative structure-activity relationship study on some matrix metalloproteinase and collagenase inhibitors.
abstract: A quantitative structure-activity relationship (QSAR) study is made on some hydroxamic acid-based inhibitors of matrix metalloproteinases (MMPs) and a bacterial collagenase, namely Clostridium histolyticum collagenase (ChC), that also belongs to an MMP family, M-31, using Kier's valence molecular connectivity index (1)chi(v) of the substituents and electrotopological state (E-state) indices of some atoms. The results indicate that out of the four MMPs (MMP-1, MMP-2, MMP-8, and MMP-9) studied, MMP-2 and MMP-9 can be structurally quite similar, but widely differing from MMP-1 and MMP-8 and ChC. For MMP-2 and MMP-9, the inhibition activity of compounds is shown to depend on both (1)chi(v )and E-state indices, while for MMP-1 and MMP-8 it is shown to depend only on E-state indices and for ChC only on (1)chi(v). However, in all the cases, an aromatic group like C(6)F(5) or 3-CF(3)-C(6)H(4) attached to SO(2) moiety in the compounds is indicated to be equally beneficial, due to probably the involvement of fluorine atom(s) in charge-charge interactions with the Zn(2+) ion of the enzymes or in the formation of the hydrogen bonds with some sites of the receptors.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani-333031, India.
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
authors.forename: S P
authors.initials: SP
authors.lastname: Gupta
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: D001555:Benzene Derivatives; D006845:Hydrocarbons, Fluorinated; D006877:Hydroxamic Acids; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D003012:Microbial Collagenase; D015032:Zinc