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�й�ҩѧ��־ 2014, Vol. 49 Issue (14) :1200-1204    DOI: 10.11669/cpj.2014.14.005
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23-�ǻ�������������������õ���ά������Ч��ϵ�����ӶԽ�ģʽ̽���о�
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2. �й�ҩ�ƴ�ѧ��Ȼҩ����������ҩЧ�����ص�ʵ���ң� �Ͼ� 210009
ZHANG Ting-ting1, BI Yi1*, CHEN Meng-meng1, ZHANG Xiao-chen1,XU Jin-yi2, WU Xiao-ming2*
1.Department of Medicinal Chemistry, Yantai University, Yantai 264005, China;
2. State Key Laboratory of National Medicines, China Pharmaceutical University, Nanjing 210009, China

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ժҪ Ŀ�� ̽�����п��������õ�23-�ǻ����������������ά������Ч��ϵģ�ͣ������������칹øI( Topo I )�ķ��ӶԽ�ģʽ������ ��ʵ��Ӧ��Topomer CoMFA����34��23-�ǻ���������������ж�����Ч��ϵ�о���������ά������Ч��ϵģ�͡��������ף�����Surflex-dock�о�23-�ǻ��������������������칹øI�ķ��ӶԽӽ��ģʽ����� Topomer CoMFAģ��q2=0.521��r2=0.873��������Ԥ�������Ϻõ���ά������ϵģ�͡�Surflex-dock�����ʾ�����������Topo I��Lys532��Arg488��Arg590��Arg364�Ȼ��Թ��ܲл�����������á����� ������ά������Ч��ϵģ��Ԥ�������Ϻã�������ָ��23-�ǻ����������������ơ����ӶԽӽ����ʾ��Topo I������Ϊ23-�ǻ�������������������Ե�DZ�ڰе����ʵ�����о���
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Abstract�� OBJECTIVE To formulate the three-dimensional quantitative structure-activity relationship (3D-QSAR) model of 23-hydroxybetulinic acid derivatives with promising antitumor activity and study their molecular docking with topoisomerase I (Topo I). METHODS Topomer CoMFA was used to analyze the quantitative structure-activity relationship of thirty-four 23-hydroxybetulinic acid derivatives, and molecular docking analysis was applied to characterize the interactions between 23-hydroxybetulinic acid derivatives and Topo I. RESULTS One satisfactory substructure-based Topomer CoMFA model (q2, 0.521; r2, 0.873) possessing predictive capability was obtained. Surflex-dock analysis displayed that the ligands and Topo I interacted with each other via several residues (such as Lys532, Arg488, Arg590 and Arg364) which had a very important effect on hydrogen bonds. CONCLUSION Topomer CoMFA combined with Surflex-dock analysis can be applied to design new 23-hydroxybetulinic acid derivatives with higher antitumor activities.
Keywords�� 23-hydroxybetulinic acid derivatives,   topomer CoMFA,   surflex-dock,   Topo I,   antitumor activity     
�ո�����: 2014-09-03;
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ZHANG Ting-Ting-, BI Yi-*, CHEN Meng-Meng- etc .3D-QSAR and Molecular Docking Studies on 23-Hydroxybetulinic Acid Derivatives with Antitumor Activity[J]  Chinese Pharmaceutical Journal, 2014,V49(14): 1200-1204
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