339365-49-0Relevant articles and documents
Lipophilicity determination of antifungal isoxazolo[3,4-b]pyridin-3(1h)-ones and their n1-substituted derivatives with chromatographic and computational methods
?uvela, Petar,Andri?, Filip,Ba?zek, Tomasz,Baranowski, Pawe?,Ciura, Krzesimir,Fedorowicz, Joanna,Greber, Katarzyna Ewa,Kawczak, Piotr,Nowakowska, Joanna,Sa?zewski, Jaros?aw
, (2019)
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.
The tandem mannich-electrophilic amination reaction: A versatile platform for fluorescent probing and labeling
Saczewski, Jaroslaw,Hinc, Krzysztof,Obuchowski, Michal,Gdaniec, Maria
, p. 11531 - 11535 (2013)
Tandem fluorogenic reaction: A new platform for the direct, selective and sensitive detection of formaldehyde and/or secondary aliphatic amines, based on a tandem Mannich-electrophilic amination reaction, is described. Biological applications of hydrophilic, water-soluble fluorescent 2,2-dialkyl-2,3-dihydro- [1,2,4]triazolo[4,3-a]pyridin-2-ium-8-carboxylates (Safarinium P probes) are exemplified by labeling of the amine-containing Ac-AKF-NH2 peptide and Bacillus subtilis spores in aqueous solution. Copyright
Cytotoxic triterpenoid–safirinium conjugates target the endoplasmic reticulum
Kraft, Oliver,Kozubek, Marie,Hoenke, Sophie,Serbian, Immo,Major, Daniel,Csuk, René
, (2020/10/15)
Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity. An exception, however, was safirinium P derived compound 30 holding low EC50 = 5.4 μM (for A375 cells) to EC50 = 7.5 μM (for FaDu cells) as well as EC50 = 6.6 μM for non-malignant fibroblasts NIH 3T3. Fluorescence imaging showed that the safirinium core structures cannot enter the cells (not even after a prolonged incubation time of 24 h), while the conjugates (as exemplified for 30) are accumulating in the endoplasmic reticulum but not in the mitochondria. The development of safirinium–hybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents.
