CoMFA Study on Anti-proliferative Activity of Fluoroquinolone Amide Derivatives  

作　　者：ENG Hui CAO Jing-Pei FENG Chang-Jun 冯惠;曹景沛;冯长君(School of Chemical Engineering and Technology,China University of Mining and Technology,Xuzhou 221116,China;Key Laboratory of Coal Processing and Efficient Utilization(Ministry of Education),Xuzhou 221116,China;School of Material&Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China)

机构地区：[1]School of Chemical Engineering and Technology,China University of Mining and Technology,Xuzhou 221116,China [2]Key Laboratory of Coal Processing and Efficient Utilization(Ministry of Education),Xuzhou 221116,China [3]School of Material&Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China

出　　处：《Chinese Journal of Structural Chemistry》2022年第3期241-247,I0014,共8页结构化学（英文）

基　　金：supported by the National Natural Science Foundation of China (21676292, 21075138);special fund of State Key Laboratory of Structure Chemistry (2016028)

摘　　要：The in vitro anti-proliferative activity(pICi,i=hp,ca,hl)of fluoroquinolone(rhodanineα,β-unsaturated ketone)amide compounds,referred to as“fluoroquinolone amide derivatives(FQADs)”towards Hep-3B,Capan-1 and HL60 cells,was studied by the 3D-QSAR method of comparative molecular field analysis(CoMFA).Based on the training set of 14 compounds,the prediction model was established,which was further verified by the test set of 5 compounds with template molecule included.It is found that steric and electrostatic fields contribute 66.8%and 33.2%to pIChp,61.4%and 38.6%to pICca,and 61.5%and 38.5%to pIChl,respectively.The Rcv 2(i.e,cross-validation coefficient)is 0.324,0.381,and 0.421 for pIChp,pICca,and pIChl,respectively,while the corresponding R2(i.e,non-cross-validation coefficient)all reach 0.999.Then,the models were employed to estimate the activities of the training and test compounds,and the results show that the stability and predictability of developed models are very satisfactory.According to the contour maps of steric and electronic fields,bulky groups linked to 2-,3-,4-positions of phenyl ring,and electropositive groups near the 4-position and electronegative groups far away may increase the anti-proliferative activity.Using the information provided by the 3D contour maps,four new FQADs owing higher antiproliferative activity were designed,but their effectiveness should be further tested by experiments.

关 键 词：fluoroquinolone amide derivatives Hep-3B cell Capan-1cell HL60 cell anti-proliferative activity comparative molecular field analysis 

分 类 号：TQ460.1[化学工程—制药化工]