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首页> 外文期刊>Drug design and discovery >QSAR of matrix metalloproteinase inhibitor N-((substituted phenyl)sulfonyl)-N-4-nitrobenzylglycine hydroxamates using LFER model.
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QSAR of matrix metalloproteinase inhibitor N-((substituted phenyl)sulfonyl)-N-4-nitrobenzylglycine hydroxamates using LFER model.

机译：使用LFER模型对基质金属蛋白酶抑制剂N-（（取代的苯基）磺酰基）-N-4-硝基苄基甘氨酸异羟肟酸酯的QSAR进行QSAR分析。

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摘要

QSAR analyses of matrix metalloproteinase (MMP) inhibitor N-[(substituted phenyl)sulfonyl]-N-4-nitrobenzylglycine hydroxamates, recently reported by Scozzafava and Supuran, have been attempted using linear free energy related (LFER) model of Hansch to explore the contribution patterns of the phenyl ring substitutions (P1' anchoring site of the ligands) to the activities against MMP-1, -2, -8 and -9 (pC1, pC2, pC, and pC9) and C. histolyticum collagenase (pC(ChC)) and also to find out relations among the activities. Multiple regression analyses applied on the data set reveal that electron withdrawing meta substituents and lipophilic ortho and meta substituents are conducive to pC1 while presence of substituents (larger than hydrogen) at vicinal positions on the phenyl ring and bulkier ortho substituents are detrimental to the activity. Again, the electronic and steric parameters of meta substituents (sigmam and MRm) and lipophilicity parameter of ortho substituents (pio) contribute significantly to pC2, pC8 and pC9: sigmam shows parabolic relationships (optimum sigmam values being 0.518, 0.584 and 0.522 respectively) and steric bulk of meta substituents has negative impact while presence of hydrophilic groups at the ortho positions increases the activities. Further, presence of electron withdrawing meta substituents and hydrophilic para substituents is conducive to the C. histolyticum collagenase (pC(ChC)) activity. The study suggests that the structural and physicochemical requirements of the P1' anchoring site for the activities against MMP-2, -8 and -9 are highly intercorrelated and these are comparatively less correlated with those for the activities against MMP-1 and C. histolyticum collagenase.
机译：最近，Scozzafava和Supuran报道了基质金属蛋白酶（MMP）抑制剂N-[（取代的苯基）磺酰基] -N-4-硝基苄基甘氨酸异羟肟酸酯的QSAR分析，已尝试使用Hansch的线性自由能相关（LFER）模型来探索环取代（配体的P1'锚定位点）对MMP-1，-2，-8和-9（pC1，pC2，pC和pC9）和解组织梭状芽孢杆菌胶原酶（pC（ ChC）），并找出活动之间的关系。对数据集进行的多元回归分析表明，吸电子的间位取代基和亲脂性邻位和间位取代基有利于pC1，而在苯环附近位置上存在取代基（大于氢）和较大的邻位取代基不利于其活性。同样，间位取代基的电子和空间参数（sigmam和MRm）和邻位取代基的亲脂性参数（pio）对pC2，pC8和pC9做出了重要贡献：sigmam显示了抛物线关系（最佳sigmam值分别为0.518、0.584和0.522）和间位取代基的空间体积具有负面影响，而邻位亲水基团的存在增加了活性。此外，吸电子的间位取代基和亲水性对位取代基的存在有利于组织溶梭菌胶原酶（pC（ChC））的活性。研究表明，针对MMP-2，-8和-9的活性，P1'锚定位点的结构和理化要求高度相互关联，而与针对MMP-1和溶血梭状芽孢杆菌的活性相关性相对较低。胶原酶。

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