Next Article in Journal
Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials
Next Article in Special Issue
A Comprehensive QSAR Study on Antileishmanial and Antitrypanosomal Cinnamate Ester Analogues
Previous Article in Journal
Chemometric Characterization of Strawberries and Blueberries according to Their Phenolic Profile: Combined Effect of Cultivar and Cultivation System
Previous Article in Special Issue
Carbon Nanotubes Having Haeckelite Defects as Potential Drug Carriers. Molecular Dynamics Simulation
Open AccessArticle

Lipophilicity Determination of Antifungal Isoxazolo[3,4-b]pyridin-3(1H)-ones and Their N1-Substituted Derivatives with Chromatographic and Computational Methods

1
Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
2
Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
3
Department of Analytical Chemistry, University of Belgrade—Faculty of Chemistry, Studentski trg 12–16, 11000 Belgrade, Serbia
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
5
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
*
Author to whom correspondence should be addressed.
Current address: Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Academic Editor: Julio Caballero
Molecules 2019, 24(23), 4311; https://doi.org/10.3390/molecules24234311
Received: 31 October 2019 / Revised: 14 November 2019 / Accepted: 21 November 2019 / Published: 26 November 2019
(This article belongs to the Special Issue Computational Methods for Drug Discovery and Design)
The lipophilicity of a molecule is a well-recognized as a crucial physicochemical factor that conditions the biological activity of a drug candidate. This study was aimed to evaluate the lipophilicity of isoxazolo[3,4-b]pyridine-3(1H)-ones and their N1-substituted derivatives, which demonstrated pronounced antifungal activities. Several methods, including reversed-phase thin layer chromatography (RP-TLC), reversed phase high-performance liquid chromatography (RP-HPLC), and micellar electrokinetic chromatography (MEKC), were employed. Furthermore, the calculated logP values were estimated using various freely and commercially available software packages and online platforms, as well as density functional theory computations (DFT). Similarities and dissimilarities between the determined lipophilicity indices were assessed using several chemometric approaches. Principal component analysis (PCA) indicated that other features beside lipophilicity affect antifungal activities of the investigated derivatives. Quantitative-structure-retention-relationship (QSRR) analysis by means of genetic algorithm—partial least squares (GA-PLS)—was implemented to rationalize the link between the physicochemical descriptors and lipophilicity. Among the studied compounds, structure 16 should be considered as the best starting structure for further studies, since it demonstrated the lowest lipophilic character within the series while retaining biological activity. Sum of ranking differences (SRD) analysis indicated that the chromatographic approach, regardless of the technique employed, should be considered as the best approach for lipophilicity assessment of isoxazolones. View Full-Text
Keywords: lipophilicity; isoxazolo[3,4-b]pyridin-3(1H)-one; isoxazolone; reversed-phase liquid chromatography; sum of ranking differences; QSRR analysis lipophilicity; isoxazolo[3,4-b]pyridin-3(1H)-one; isoxazolone; reversed-phase liquid chromatography; sum of ranking differences; QSRR analysis
Show Figures

Figure 1

MDPI and ACS Style

Ciura, K.; Fedorowicz, J.; Andrić, F.; Žuvela, P.; Greber, K.E.; Baranowski, P.; Kawczak, P.; Nowakowska, J.; Bączek, T.; Sączewski, J. Lipophilicity Determination of Antifungal Isoxazolo[3,4-b]pyridin-3(1H)-ones and Their N1-Substituted Derivatives with Chromatographic and Computational Methods. Molecules 2019, 24, 4311.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop