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 1χv 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 1χv 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 1χv. However, in all the cases, an aromatic group like C6F5 or 3-CF3–C6H4 attached to SO2 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 Zn2+ ion of the enzymes or in the formation of the hydrogen bonds with some sites of the receptors.