A comparative QSAR study on carbonic anhydrase and matrix metalloproteinase inhibition by sulfonylated amino acid hydroxamates.
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 1chi(v) 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 C6F5 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 Zn2+ ion present in the catalytic site of both families of enzymes.
Gupta
S P
SP
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, India. spg@bits-pilani.ac.in
Maheswaran
V
V
Pande
V
V
Kumar
Dalip
D
D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D002257:Carbonic Anhydrase Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors