整合素αvβ3小分子拮抗药的二维定量构效关系  

2D-QSAR studies of integrin αvβ3 antagonists

作　　者：林克江[1] 黄振桂[1] 黄敏[1] 王舒[1] 韩沐芮[1] 李鹃利[1] 唐翊铭[1] 

机构地区：[1]中国药科大学药物化学教研室,南京210009

出　　处：《中国药科大学学报》2012年第6期502-507,共6页Journal of China Pharmaceutical University

摘　　要：整合素αvβ3在肿瘤组织中的新生血管内皮细胞膜有高度特异性表达,在静息期的内皮细胞以及大部分正常器官系统缺失表达,当其功能受到抑制时,血管内皮细胞凋亡,肿瘤生长受到抑制。通过对20个非肽类整合素αvβ3小分子拮抗药进行二维定量构效关系研究,发现整合素αvβ3小分子拮抗药的活性与零阶价分子连接性指数、偶极矩、最大正电荷、最大负电荷存在良好的线性关系(r=0.91),获得较好的定量构效关系方程,并经分子对接验证,为进一步设计合成新的非肽类小分子提供理论指导。The integrin αvβ3 is expressed in activated endothelial cells as well as some tumor cells while there is less expressed in resting endothelial cells and most normal organ systems.When it is inhibited,vascular endothelial cell apoptosis increase and tumor growth are restrained.Two-dimensional quantitative structure-activity relationship（2D-QSAR） study was performed on 20 integrin αvβ3 non-peptide small molecule antagonists.The results showed that the biological activities were closely related to the zero-order molecular connectivity index,dipole moments,the largest positive charge and negative charge.The reasonable 2D-QSAR equation was achieved（r=0.91） and validated by the molecular docking to provide theoretical guidance for further design and synthesis of new non-peptide small molecule antagonists.

关 键 词：整合素αvβ3抑制剂 非肽类小分子拮抗药 二维定量构效关系 

分 类 号：R914[医药卫生—药物化学]