氟喹诺酮均三唑稠杂环类衍生物抗肿瘤活性理论研究

发布时间：2019-06-24 13:54

【摘要】：为了探讨氟喹诺酮均三唑稠杂环类衍生物(FQTHs)体外抗肿瘤作用的微观机理,建立其对中国仓鼠卵巢细胞(CHO)、鼠白血病细胞(L1210)和人白血病细胞(HL60)等的体外抗肿瘤活性(A_j:A_C、A_L、A_H)与量化参数Q_t的定量结构-活性相关性(QSAR)模型。采用半经验计算法MOPAC-AM1计算15种化合物的量化参数(Qt,如E_(HOMO)、E_(LUMO)、μ、Q_(Cd)、Q_(Ne)、Q_(Of)、Q_F、Q_S等)。运用最佳变量子集回归方法建立FQTHs体外抗肿瘤活性的QSAR模型。A_C的最佳三元线性回归模型的判定系数R~2和逐一剔除法交叉验证系数R_(cv)~2分别为0.910和0.827,A_L对应的R~2和R_(cv)~2分别为0.874和0.815,A_H对应的R~2和R_(cv)~2分别为0.941和0.894。通过R~2、R_(adj)~2、F、R_(cv)~2、V_(IF)、A_(IC)、F_(IT)等检验证明上述模型具有稳健性和预测能力。模型显示Q_(Cd)、Q_(Ne)、Q_(Of)和μ直接影响15种化合物的生物活性。
[Abstract]:In order to study the micro-mechanism of the in vitro anti-tumor effect of the three-membered fused heterocyclic derivative (HTHs), the anti-tumor activity (A _ j: A _ C, A _ L) in Chinese hamster ovary cells (CHO), murine leukemia cells (L1210) and human leukemia cells (HL60) was established. A _ H) and the quantitative structure-activity correlation (QSAR) model of the quantization parameter Q _ t. The quantitative parameters (Qt, such as E _ (HOMO), E _ (LUMO),[mu], Q _ (Cd), Q _ (Ne), Q _ (Of), Q _ F, Q _ S, etc.) of 15 compounds are calculated by means of semi-empirical calculation (MOPAC-AM1). The QSAR model of anti-tumor activity in vitro was established by using the optimal variable subset regression method. The R ~ 2 and R _ (cv) ~ (2) and R _ (cv) ~ (2) ~ (2) and R _ (cv) ~ (2) ~ (2) ~ (2) and R _ (cv) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) ~ (2) and R _ (cv) ~ (2) ~ (2) ~ (2) and R _ (cv) ~ (2) ~ (2) ~ (2) ~ ( The results of R ~ 2, R _ (adj) ~ 2, F, R _ (cv) ~ 2, V _ (IF), A _ (IC), and F _ (IT) prove that the model is robust and predictive. The model shows that Q _ (Cd), Q _ (Ne), Q _ (Of) and. mu. directly affect the biological activity of 15 compounds.
【作者单位】：徐州工程学院化学化工学院;徐州医学院附属医院心内科;
【基金】：国家自然科学基金(21075138) 结构化学国家重点实验室开放基金(20160028) 徐州工程学院科研项目(XKY2012307;XKY2013103)
【分类号】：R96

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