氟喹诺酮三唑酮衍生物抗增殖活性的CoMFA模型

CoMFA Model of Anti-proliferative Activities of Fluoroquinolone Triazolone Derivatives Against Human Leukemia HL60 Cells

应用比较分子力场分析法(CoMFA)研究了18种氟喹诺酮三唑啉酮衍生物对人白血病HL60细胞的体外抗增殖活性(pH)。建立的模型在高相关系数值(R2=0.969)和交叉验证系数值(R2cv=0.473)方面显示出良好的相关和预测能力。空间场和静电场对pH的贡献分别为58.5%和41.5%。基于CoMFA等高线图,揭示了该系列化合物抗增殖活性的一些关键结构因素,如疏水作用、空穴契合、库仑力及氢键等。这些结果为理解其作用机制、设计具有高抗增殖活性的新型氟喹诺酮三唑啉酮类化合物以及预测其活性提供了有益的理论参考。

The comparative molecular force field analysis(CoMFA)method was applied to systematically study the in vitro anti-proliferative activities(pH)of 18 fluoroquinolone triazolone derivatives against human leukemia HL60 cells.The established CoMFA model showed good correlative and predictive ability in terms of high correlation coefficient value(R2=0.969)and cross-validation coefficient value(Rcv2=0.473).The contributions of steric and electrostatic fields was 58.5%and 41.5%,respectively.Based on the CoMFA contour maps,some key structural factors(such as hydrophobic factor,steric fit,Coulomb force and hydrogen bonds etc.)responsible for the anti-proliferative activity of the series of compounds were revealed.The results provide some useful theoretical references for understanding the mechanism of action,designing new fluoroquinolone triazolone compounds with high anti-proliferative activity,and predicting their activities.