A Comparative QSAR Study on Carbonic Anhydrase and Matrix Metalloproteinase Inhibition by Sulfonylated Amino Acid Hydroxamates
A Comparative QSAR Study on Carbonic Anhydrase and Matrix Metalloproteinase Inhibition by Sulfonylated Amino Acid Hydroxamates
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DOI：
10.1080/1475636021000049735
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发表时间：
2003-01
影响因子：
5.6
通讯作者：
S.P. Gupta;V. Maheswaran;V. Pande;Dalip Kumar
中科院分区：
文献类型：
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作者：
S.P. Gupta;V. Maheswaran;V. Pande;Dalip Kumar
用定量构效关系（QSAR）研究了磺酰化氨基酸异羟肟酸盐对碳酸酐酶（CA）和基质金属蛋白酶（MMPs）的几种同工酶的抑制作用。对于这两种酶，异羟肟酸酯的抑制效力被发现与Kier的一阶价分子连接性指数1 × v的分子和一些原子的电拓扑状态指数很好地相关。从结果中，它表明，而羟肟酸-CA结合可能涉及主要是极性相互作用，羟肟酸-MMP和羟肟酸-ChC（ChC：梭菌溶组织胶原酶，另一种锌酶相关的MMP）的结合可能涉及一些疏水相互作用。MMPs和ChC都具有与CA中相应位点性质完全相反的电子位点。一个基团，如C6 F 5存在于磺酰基部分被证明是有利的CA和MMP（也ChC）抑制，这是由于该基团与Zn 2+离子存在于两个家族的酶的催化位点的相互作用。
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.