Browsing by Author "Gupta, S.P."

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    A Comparative QSAR Study on Carbonic Anhydrase and Matrix Metalloproteinase Inhibition by Sulfonylated Amino Acid Hydroxamates
    (Taylor & Francis, 2008-09-30) Kumar, Dalip; Gupta, S.P.
    A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc-containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier's first-order valence molecular connectivity index 1χv of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C 6 F 5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn 2+ ion present in the catalytic site of both families of enzymes.
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    A quantitative structure–activity relationship study on some matrix metalloproteinase and collagenase inhibitors
    (Elsiever, 2003-02-06) Kumar, Dalip; Gupta, S.P.
    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.