Abstract
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.
Highlights
Lipophilicity is one of the essential factors that determine the biological activity of drug candidates.It determines the transport of molecules through biological membranes and their ability to undergo complexation with blood proteins and binding to receptors [1]
Taking into from a medicinal chemistry perspective, the Taking into account accountthe theimportance importanceofoflipophilicity lipophilicity from a medicinal chemistry perspective, present study focuses on on comparing the determination the present study focuses comparing theperformance performanceofofmethods methodsfor for lipophilicity lipophilicity determination with regard to the aforementioned group of drugs candidates
These results indicate that the established models can be successfully used for prediction on chromatographic indexes of pyrido-isoxazolone derivatives based on the computational descriptors
Summary
Lipophilicity is one of the essential factors that determine the biological activity of drug candidates. It determines the transport of molecules through biological membranes and their ability to undergo complexation with blood proteins and binding to receptors [1]. According to the International Union of Pure and Applied Chemistry (IUPAC), the operational definition of lipophilicity is the affinity of a molecule or a moiety for a lipophilic environment. It is commonly measured by its distribution behavior in a biphasic system, either a liquid–liquid or solid–liquid system [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
