一系列双DNA旋切酶和拓扑异构酶IV抑制剂的亲脂性的高效液相色谱评价和QSRR建模

IF 1.7 4区化学 Q3 CHEMISTRY, ANALYTICAL

Acta Chromatographica Pub Date : 2022-12-05 DOI:10.1556/1326.2022.01096

V. Dobričić, J. Savić, T. Tomašič, Martina Durcik, Nace Zidar, L. P. Mašič, J. Ilaš, D. Kikelj, O. Čudina

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引用次数: 0

摘要

细菌DNA回转酶和拓扑异构酶IV控制着DNA在复制过程中的拓扑状态，是重要的抗菌药物靶点。为了成为成功的候选药物，新合成的化合物必须具有最佳的亲脂性，从而能够有效地递送到作用部位。以C8色谱柱和乙腈/磷酸盐缓冲液(pH 5.5和pH 7.4)为流动相，采用反相高效液相色谱(RP-HPLC)对23种合成的双DNA旋切酶和拓扑异构酶IV抑制剂的保留行为进行了研究。在两种pH值下计算logD，保留参数φ0与logD的相关性最好，表明该体系可替代摇瓶法测定亲脂性。随后的QSRR分析显示，内在亲脂性(logP)和分子量(bcutp3)对该保留参数有正影响，而溶解度(bcutp3)对该保留参数有负影响。

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High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this retention parameter.

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来源期刊

Acta Chromatographica 化学-分析化学

CiteScore

4.00

自引率

0.00%

发文量

审稿时长

2.3 months

期刊介绍： Acta Chromatographica Open Access Acta Chromatographica publishes peer-reviewed scientific articles on every field of chromatography, including theory of chromatography; progress in synthesis and characterization of new stationary phases; chromatography of organic, inorganic and complex compounds; enantioseparation and chromatography of chiral compounds; applications of chromatography in biology, pharmacy, medicine, and food analysis; environmental applications of chromatography; analytical and physico-chemical aspects of sample preparation for chromatography; hyphenated and combined techniques; chemometrics and its applications in separation science.