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

Dobričić, Vladimir (author), Savić, Jelena (author), Tomašič, Tihomir (author), Durcik, Martina (author), Zidar, Nace (author), Peterlin-Mašič, Lucija (author), Ilaš, Janez (author), Kikelj, Danijel (author), Čudina, Olivera (author)

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.

• Language: English
• Keywords: RP-HPLC, DNA gyrase and topoisomerase IV inhibitors, lipophilicity prediction, PLS, MLR models, SVM models
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 45-51
• Numbering: Vol. 36, no. 1
• PID: 20.500.12556/RUL-165210
• UDC: 543.544.5:615.28
• ISSN on article: 2083-5736
• DOI: 10.1556/1326.2022.01096
• COBISS.SI-ID: 132432387
• Publication date in RUL: 27.11.2024

Record is a part of a journal

• Title: Acta Chromatographica
• Shortened title: Acta Chromatogr.
• Publisher: Institute of Chemistry, University of Silesia
• ISSN: 2083-5736
• COBISS.SI-ID: 4913016

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: protibakterijska zdravila, zaviralci topoizomeraze IV, bakterijska DNA giraza, tekočinska kromatografija visoke ločljivosti, zdravila, tekočinska kromatografija