Gupta S P, Maheswaran V, Pande V, Kumar Dalip
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, India.
J Enzyme Inhib Med Chem. 2003 Feb;18(1):7-13. doi: 10.1080/1475636021000049735.
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.
对磺酰化氨基酸异羟肟酸酯抑制碳酸酐酶（CA）的几种同工酶和一些基质金属蛋白酶（MMP）进行了定量构效关系（QSAR）研究，这两类酶均为含锌酶家族。对于这两种酶，发现异羟肟酸酯的抑制效力与分子的基尔一阶价分子连接性指数1χ(v)以及某些原子的电子拓扑状态指数密切相关。从结果来看，表明异羟肟酸酯与CA的结合可能主要涉及极性相互作用，而异羟肟酸酯与MMP以及异羟肟酸酯与溶组织梭菌胶原酶（ChC：与MMP相关的另一种锌酶）的结合可能涉及一些疏水相互作用。MMP和ChC还具有一些性质与CA中相应位点完全相反的电子位点。磺酰基部分中存在的如C6F5这样的基团在CA和MMP（以及ChC）抑制中均显示出优势，这被认为是由于该基团与这两类酶催化位点中存在的Zn2+离子相互作用所致。
