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

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4311 ◽  
Author(s):  
Krzesimir Ciura ◽  
Joanna Fedorowicz ◽  
Filip Andrić ◽  
Petar Žuvela ◽  
Katarzyna Ewa Greber ◽  
...  
Keyword(s):  
Biological Activity ◽  
High Performance ◽  
Density Functional ◽  
Principal Component ◽  
Reversed Phase ◽  
Drug Candidate ◽  
Antifungal Activities ◽  
Physicochemical Descriptors ◽  
Sum Of Ranking Differences ◽  
Layer Chromatography

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.

scholarly journals Lipophilicity assessment of some 5,5-disubstituted hydantoins by the means of reversed phase liquid chromatography

2013 ◽  
Vol 19 (1) ◽  
pp. 1-6
Author(s):  
Vesna Despotovic ◽  
Nemanja Trisovic ◽  
Anamarija Mandic ◽  
Gordana Uscumlic ◽  
Tatjana Djakovic-Sekulic
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Principal Component ◽  
Reversed Phase ◽  
Retention Data ◽  
Reversed Phase Liquid Chromatography ◽  
Mobile Phases ◽  
Statistical Level ◽  
Phase Liquid ◽  
Layer Chromatography

The retention of some 5,5-disubstituted hydantoins was investigated by reversed phase high performance thin-layer chromatography (RP HPTLC) and reversed phase high-pressure liquid chromatography (RP HPLC). The mobile phases were mixtures of methanol-water and acetonitrile-water in various volume fractions. In order to explore and visualize similarities and differences among the investigated compounds and chromatographic system Principal Component Analysis (PCA) was used. Results show that the experimental lipophilicity indices estimated from retention data (RM,W, logkw) and PC1 are directly correlated with logP values at a high significant statistical level.

211 REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AS A TOOL TO ELUCIDATE THE BIOLOGICAL ACTIVITY OF COMMERCIAL EQUINE CHORIONIC GONADOTROPIN (eCG)

2014 ◽  
Vol 26 (1) ◽  
pp. 219
Author(s):  
R. H. Alvarez ◽  
B. E. Almeida ◽  
M. T. C. P. Ribela ◽  
F. L. N. Natal ◽  
A. J. F. Melo ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Biological Activity ◽  
High Performance ◽  
Ovarian Response ◽  
Reversed Phase ◽  
Chemical Profile ◽  
Ovarian Weight ◽  
Rp Hplc ◽  
Physical Chemical ◽  
Equine Chorionic Gonadotropin

Superovulation in ruminants can be induced with a single injection of equine chorionic gonadotropin (eCG). However, ovarian response is sometimes lower than expected because of, among other factors, the source of eCG used. This study aimed at establishing the physical-chemical profile of commercial eCG, in order to find differences which can be related to their biological activity. Four different commercial eCG products for veterinary use (A, B, C, D) and one eCG chemical reagent from Sigma (St. Louis, MO, USA), here used as reference preparation, were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC) using a C4-Grace Vydac 214 TP 54-column (25 cm × 4.6 mm I.D.), with UV detection at 220 nm. All eCG preparations presented at least three peaks with retention times (tR) of ~27(I), 34(II), and 36(III) minutes, with a peak at tR = 27 min common to A, C, D, and Sigma eCG, whereas preparation B did not present this peak. A bioassay test was carried with all of these preparations. Immature 21- to 25-day-old Wistar female rats received the equivalent to 10 IU of eCG of each one of these preparations. Autopsy was performed 48 h later and ovaries were removed and weighed. The average ovarian weight for preparations A, C, D, and Sigma were ~0.0795 ± 0.0107 g, whereas preparation B was 0.035 ± 0.007 g (P < 0.01). Preparation B was not different from saline (0.034 ± 0.002 g). In order to establish which one of these three peaks presented the highest biological activity, a mass equivalent to 10 IU of eCG from peaks I, II, and III of Sigma and of product A were studied. The average ovarian weight of animals injected with material from peak II and III (~0.0285 ± 0.003 g) were similar to that of the control whereas peak I produced ovarian weights of 0.059 ± 0.007 g and 0.075 ± 0.010 g for Sigma and product A, respectively (P < 0.01). These results suggest that the lack of ovarian response to eCG treatments can be related to differences in the physical-chemical profile of commercial eCG products and that RP-HPLC is a fast and reliable tool for detecting these differences. Supported by FAPESP (Grant 11/13096-0).

Preparative reversed-phase high-performance thin-layer chromatography for analysis of anthocyanins

2006 ◽  
Vol 19 (112) ◽  
pp. 463-466 ◽  
Author(s):  
Agnieszka Skalska ◽  
Anna Matysik ◽  
Marek Gerkowicz ◽  
Magdalena Wójciak-Kosior
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Reversed Phase ◽  
Layer Chromatography

scholarly journals Separation of 9-Fluorenylmethyloxycarbonyl Amino Acid Derivatives in Micellar Systems of High-Performance Thin-Layer Chromatography and Pressurized Planar Electrochromatography

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Beata Polak ◽  
Adam Traczuk ◽  
Sylwia Misztal
Keyword(s):  
Amino Acid ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Mobile Phase ◽  
High Performance ◽  
Reversed Phase ◽  
Amino Acid Derivatives ◽  
Solute Retention ◽  
Micellar Systems ◽  
Layer Chromatography

AbstractThe problems with separation of amino acid mixtures in reversed-phase mode are the result of their hydrophilic nature. The derivatisation of the amino group of mentioned above solutes leads to their solution. For this purpose, 9-fluorenylmethoxycarbonyl chloroformate (f-moc-Cl) as the derivatisation reagent is often used. In our study, the separation of some f-moc- amino acid derivatives (alanine, phenylalanine, leucine, methionine, proline and tryptophan) with the use of micellar systems of reversed-phase high-performance thin-layer chromatography (HPTLC) and pressurized planar electrochromatography (PPEC) is investigated. The effect of surfactant concentration, its type (anionic, cationic and non-ionic) and mobile phase buffer pH on the discussed above solute migration distances are presented. Our work reveals that the increase of sodium dodecylsulphate concentration in the mobile phase has a different effect on solute retention in HPTLC and PPEC. Moreover, it also affects the order of solutes in both techniques. In PPEC, in contrast to the HPTLC technique, the mobile phase pH affects solute retention. The type of surfactant in the mobile phase also impacts solute retention and migration distances. A mobile phase containing SDS improves system efficiency in both techniques. Herein, such an effect is presented for the first time.

scholarly journals Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock

2020 ◽  
Vol 65 (1) ◽  
pp. e01385-20
Author(s):  
T. Parks Remcho ◽  
Sravanthi D. Guggilapu ◽  
Phillip Cruz ◽  
Glenn A. Nardone ◽  
Gavin Heffernan ◽  
...  
Keyword(s):  
Active Site ◽  
Antimalarial Drug ◽  
High Performance ◽  
Drug Candidate ◽  
Resonance Spectroscopy ◽  
Content Type ◽  
Computational Docking ◽  
Layer Chromatography ◽  
Commercial Stock ◽  
Selection Of

ABSTRACTWR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing the human dhfr gene have become valued tools for the genetic modification of parasites in the laboratory. Concerns over the ineffectiveness of WR99210 from some sources encouraged us to investigate the biological and chemical differences of supplies from two different companies (compounds 1 and 2). Compound 1 proved effective at low nanomolar concentrations against Plasmodium falciparum parasites, whereas compound 2 was ineffective, even at micromolar concentrations. Intact and fragmented mass spectra indicated identical molecular formulae of the unprotonated (free base) structures of compounds 1 and 2; however, the compounds displayed differences by thin-layer chromatography, reverse-phase high-performance liquid chromatography, and UV-visible spectroscopy, indicating important isomeric differences. Structural evaluations by 1H, 13C, and 15N nuclear magnetic resonance spectroscopy confirmed compound 1 as WR99210 and compound 2 as a dihydrotriazine regioisomer. Induced fit computational docking models showed that compound 1 binds tightly and specifically in the P. falciparum DHFR active site, whereas compound 2 fits poorly to the active site in loose and varied orientations. Stocks and concentrates of WR99210 should be monitored for the presence of regioisomer 2, particularly when they are not supplied as the hydrochloride salt or are exposed to basic conditions that may promote rearrangement. Absorption spectroscopy can serve for assays of the unrearranged and rearranged triazines.

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