A 3D-QSAR Study of Catechol-O-
A 3D-QSAR Study of Catechol-O-
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儿茶酚-O- 的 3D-QSAR 研究
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发表时间：
2007-08
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通讯作者：
Chunzhi Ai, Yonghua Wang , Yan
中科院分区：
文献类型：
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作者：
Chunzhi Ai, Yonghua Wang , Yan
儿茶酚- o -甲基转移酶（COMT）抑制剂在帕金森病（PD）的治疗中发挥重要作用。采用一种新的三维定量构效关系（3D QSAR）分析方法来关联分子场和抑制百分比值。方法采用比较分子场分析（CoMFA）和比较分子相似指数分析（CoMSIA）方法，对36种已报道的COMT抑制剂进行预测。结果CoMFA模型和CoMSIA模型的交叉验证rncv2分别为0.585和0.528，而常规rncv2分别为0.979和0.891。疏水场CoMSIA模型的rncv2分别为0.544和0.930。结论对这些模型生成的三维轮廓进行单独检查有助于了解分子结构修饰的可能区域，从而提高抑制生物活性。三维QSAR模型可用于设计和预测新的COMT抑制剂。
AIM Inhibitors of Catechol-O-methyltransferase (COMT) play an important role in the treatment of Parkinson Disease (PD). A new three-dimensional quantitative structure-activity relationship (3D QSAR) analysis was performed to correlate the molecular fields and percent inhibition values. METHOD three predictive models were derived based on 36 previously reported COMT inhibitors employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. RESULT The CoMFA model and CoMSIA model with steric and electrostatic field yielded cross-validated rcv2 0.585 and 0.528 respectively whereas the conventional rncv2 were 0.979, and 0.891. The CoMSIA model with hydrophobic field exhibited rcv2 0.544 and rncv2 0.930. CONCLUSION The individual inspection of 3D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. 3D QSAR models may be useful in designing and predicting novel COMT inhibitors.
Keywords: Catechol-O-methyltransferase; inhibitor; quantitative structure-activity relationships (QSAR); comparative molecular field analysis (CoMFA); comparative molecular similarity indices analysis (CoMSIA)