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

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

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.

• Jezik: Angleški jezik
• Ključne besede: RP-HPLC, DNA gyrase and topoisomerase IV inhibitors, lipophilicity prediction, PLS, MLR models, SVM models
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 45-51
• Številčenje: Vol. 36, no. 1
• PID: 20.500.12556/RUL-165210
• UDK: 543.544.5:615.28
• ISSN pri članku: 2083-5736
• DOI: 10.1556/1326.2022.01096
• COBISS.SI-ID: 132432387
• Datum objave v RUL: 27.11.2024

Gradivo je del revije

• Naslov: Acta Chromatographica
• Skrajšan naslov: Acta Chromatogr.
• Založnik: Institute of Chemistry, University of Silesia
• ISSN: 2083-5736
• COBISS.SI-ID: 4913016

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: protibakterijska zdravila, zaviralci topoizomeraze IV, bakterijska DNA giraza, tekočinska kromatografija visoke ločljivosti, zdravila, tekočinska kromatografija