The syntheses of (2E)-2-methyl-3-(4-([4-(quinolin-2-ylmethoxy)phenyl]sulfanyl)phenyl) prop-2-enoic acid (VUFB 20609) and racemic 2-methyl-3-(4-([4-(quinolin-2-ylmethoxy) phenyl]sulfanyl)phenyl)propanoic acid (VUFB 20584) as new potential antileukotrienic drugs are described. Due to a low reactivity of the 4-substituted aryl bromides (coupling of the 4-substituted aryl bromides do not provide an activating functional group with 4-methoxybenzene-1-thiol), special conditions, in particular specific heterogeneous copper catalysts, were used. Catalytic hydrogenation of the conjugated double bond on Pd/C in the presence of the sulfanyl group is discussed. In-vitro cytotoxicity testing was performed using a microplate colorimetric acid phosphatase assay. Antiplatelet activity was evaluated using an in-vitro test in human platelet-rich plasma. Some substances inhibited arachidonic acid-induced platelet aggregation.

• MeSH
• antagonisté leukotrienů chemická syntéza   chemie   farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• chinoliny chemická syntéza   chemie   farmakologie   MeSH
• hydrogenace MeSH
• inhibitory agregace trombocytů chemická syntéza   chemie   farmakologie   MeSH
• kyselina arachidonová antagonisté a inhibitory   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• stereoizomerie MeSH
• sulfidy chemická syntéza   chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-methyl-3-(4-((4-(quinolin-2-ylmethoxy) phenyl)sulfanyl)phenyl)propanoic acid MeSH Prohlížeč
• 2-methyl-3-(4-((4-(quinolin-2-ylmethoxy)phenyl)sulfanyl)phenyl) prop-2-enoic acid MeSH Prohlížeč
• antagonisté leukotrienů MeSH
• chinoliny MeSH
• inhibitory agregace trombocytů MeSH
• kyselina arachidonová MeSH
• sulfidy MeSH

Antimycobacterial activity of phenyl salicylates (salols) was studied in connection with antituberculotic activity of salicylic derivatives. Phenyl salicylates are esters. Our attention was previously oriented on amides. Phenyl salicylates (salols) represent a new group of antimycobacterial compounds. They are less active than the corresponding amides. The most active compound in the group under study is substituted on phenyl in the salicyl moiety with a 4-methoxy group. The study reports a new item of information about antimycobacterial salicylic derivatives.

• MeSH
• antituberkulotika chemie   farmakologie   MeSH
• Mycobacterium účinky léků   MeSH
• salicylany chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antituberkulotika MeSH
• phenyl salicylate MeSH Prohlížeč
• salicylany MeSH

Four phenyl-bonded stationary phases, differing in polar embedded group between spacer and phenyl ring, were used for the separation of flavonoids in reversed-phase conditions. In addition, the work was focused on the comparison of these stationary phases in terms of retention and nature of interactions between flavonoid solutes and both, mobile and stationary phases. The differences and similarities between the columns and between individual flavonoids were evaluated by a statistical analysis. The retention over the wider range of mobile phase composition was described using well known model suggested for partition chromatographic systems. Due to differences in polarity of flavonoids, gradient elution had to be applied to achieve appropriate conditions for the successful separation. A chromatographic optimization software was employed for establish the appropriate profiles of gradient separations using UV detection at 275 nm. The most appropriate conditions for the separation of flavonoids were apparent on the phenyl and phenoxy columns.

• Klíčová slova
• Flavonoid, Glycoside, Linear free energy relationship, Phenyl-bonded phases,
• MeSH
• chemické techniky analytické metody   normy   MeSH
• chromatografie kapalinová * MeSH
• flavonoidy analýza   chemie   MeSH
• indikátory a reagencie chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• flavonoidy MeSH
• indikátory a reagencie MeSH

A series of racemic 3-phenyl-5-methyl-2H,5H-furan-2-ones related to a natural product, (-)incrustoporine, was synthesized, and their antifungal activity evaluated. The key structural feature, furanone ring, was closed via H2SO4-mediated cyclization of 2-phenylpent-4-enoic acids. The compounds displayed antifungal activity, especially against filamentous fungi. Expressed as the minimum inhibition concentration (MIC) in micromol/L, the activity of the most promising derivative against Absidia corymbifera matched that of ketoconazole (31.25 micromol/L). In terms of microg/mL, the substance was more active (7.6 microg/mL) than this standard antifungal drug (16.6 microg/mL).

• MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• chlorbenzeny chemická syntéza   chemie   farmakologie   MeSH
• cyklizace MeSH
• gama-butyrolakton analogy a deriváty   chemická syntéza   chemie   farmakologie   MeSH
• houby účinky léků   MeSH
• ketokonazol farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• racionální návrh léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-(3,4-dichlorophenyl)-5-methyl-2H,5H-furan-2-one MeSH Prohlížeč
• antifungální látky MeSH
• chlorbenzeny MeSH
• gama-butyrolakton MeSH
• incrustoporin MeSH Prohlížeč
• ketokonazol MeSH

The in vitro antifungal activity of several N2-phenyl-3(2H)-isothiazolones substituted at C4 of the phenyl moiety with heterocyclic nucleus or groups of different physico-chemical properties against four human pathogenic fungi was determined by broth macrodilution method; results were compared with those obtained with itraconazole and ketoconazole. These isothiazolones showed moderate to high activity against some or all tested strains and in comparison with the reference drugs, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g), 5-chloro-2-phenylisothiazol-3-one (1c), 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]-1,4-dihydrotriazol-5-one (1s) and 2-(4-nitrophenyl)isothiazol-3-one (2g) against Aspergillus niger, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g) and 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]piperazine-1-carboxamide (1q) against Trichophyton mentagrophytes had comparable activity, compounds 1g and 2g showing higher activity against Microsporum canis. Antifungal activity was favored by the presence of chlorine at C5 of the isothiazolone and/or the presence of nitro group or heterocyclic nucleus at C4 of the phenyl ring and proper hydrophilicity of the molecule.

• MeSH
• antifungální látky chemie   farmakologie   MeSH
• Ascomycota účinky léků   MeSH
• itrakonazol farmakologie   MeSH
• ketokonazol farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• thiazoly chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 3-isothiazolone MeSH Prohlížeč
• antifungální látky MeSH
• itrakonazol MeSH
• ketokonazol MeSH
• thiazoly MeSH

Amino acids (AAs) are minor compounds occurring in meads contributing to their final organoleptic properties. Determination of AAs profile and content can help to assess the mead authenticity, adulteration and thus its quality. This work deals with the optimization of rapid analysis of 21 AAs present in mead using reversed-phase high performance liquid chromatography with spectrophotometric detection after simple derivatization procedure with phenyl isothiocyanate agent without any sample pre-treatment. Optimized derivatization and separation conditions have been successfully applied to the quantification of AAs present in five Czech meads using the multiple point standard addition method. The total amino acid content was in the range of 134-828 mg/L. The content of proline was confirmed by Harmonised spectrophotometric method. Both chromatographic and spectrophotometric methods provided overlapping results in the range of 30-266 mg/L.

• Klíčová slova
• Amino acids, Derivatization, HPLC, Mead, Phenyl isothiocyanate (PITC),
• MeSH
• alkoholické nápoje analýza   MeSH
• aminokyseliny analýza   MeSH
• chromatografie s reverzní fází MeSH
• isothiokyanatany analýza   MeSH
• referenční standardy MeSH
• reprodukovatelnost výsledků MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• aminokyseliny MeSH
• isothiokyanatany MeSH
• phenylisothiocyanate MeSH Prohlížeč

We report first-principles calculations of the linear and nonlinear optical susceptibilities of 3-phenylamino-4-phenyl-1,2,4-triazole-5-thione crystals. The X-ray diffraction structural data of Wang et al. (Molecules 2009, 14, 608.) was used as the starting point of the computational optimization calculation by minimization of the forces acting on the atoms, and the optimized geometry was used to calculate the linear and nonlinear optical susceptibilities. We have employed the full potential linear augmented plane wave (FPLAPW) method within density functional theory (DFT) along with the Engel-Vosko exchange correlation potential. The full potential calculations show that this crystal possesses an indirect energy gap of 3.1 eV. The compound exhibits some uniaxial dielectric anisotropy resulting in a strong birefringence. The 3-phenylamino-4-phenyl-1,2,4-triazole-5-thione crystal possesses high second harmonic generation with several nonzeroth components, but only one component, chi(111)((2))(omega), is dominant and its second-order optical susceptibility of the total real part and the total absolute value at zero frequency is equal to 0.097 x 10(-7) esu.

• MeSH
• algoritmy MeSH
• chemické modely MeSH
• difrakce rentgenového záření MeSH
• thiazoly chemie   MeSH
• thioketony chemie   MeSH
• triazoly chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,2,4-triazole MeSH Prohlížeč
• 3-phenylamino-4-phenyl-1,2,4-triazole-5-thione MeSH Prohlížeč
• thiazoly MeSH
• thioketony MeSH
• triazoly MeSH

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.

• Klíčová slova
• Antimalarial activity, G-quadruplex, antileishmanial activity, antitrypanosomal activity, quinoline-like derivatives,
• MeSH
• antiprotozoální látky chemická syntéza   chemie   farmakologie   MeSH
• buňky Hep G2 MeSH
• chinoliny chemická syntéza   chemie   farmakologie   MeSH
• Leishmania donovani účinky léků   MeSH
• lidé MeSH
• Plasmodium falciparum účinky léků   MeSH
• racionální návrh léčiv * MeSH
• Trypanosoma brucei brucei účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiprotozoální látky MeSH
• chinoliny MeSH

We have synthesized a series of 2-phenyl-3-hydroxy-4(1H)-quinolinone derivatives substituted with one or more fluorine atoms on the quinolone backbone as well as on phenyl ring. The derivatives bearing more fluorine atoms were subjected to modification by nucleophilic substitutions by thiophenol, morpholine, and piperazine derivative. We have tested the prepared compounds in cytotoxic activity assay against cancer cell lines. Four derivatives exhibited micromolar values of IC50 against some of the cancer cell lines, and we have subjected them to cell cycle analysis on CCRF-CEM. Moreover, most active 7-fluoro-3-hydroxy-2-phenyl-6-(phenylthio)quinolin-4(1H)-one inhibits mitosis progression. Cell cycle analysis, in vitro tubulin polymerization assay, and tubulin imaging in cells indicated that the anticancer activity of thiophenol derivative is associated with its ability to inhibit microtubule formation.

• Klíčová slova
• 2-Phenyl-3-hydroxy-4(1H)-Quinolinone, Cytotoxic activity, Fluorine implementation, Tubulin,
• MeSH
• chinolony chemická syntéza   chemie   farmakologie   MeSH
• halogenace MeSH
• HCT116 buňky MeSH
• lidé MeSH
• modulátory tubulinu chemická syntéza   chemie   farmakologie   MeSH
• molekulární struktura MeSH
• polymerizace účinky léků   MeSH
• tubulin metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinolony MeSH
• modulátory tubulinu MeSH
• tubulin MeSH

Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.

• MeSH
• aminochinoliny chemie   farmakokinetika   farmakologie   MeSH
• Caco-2 buňky MeSH
• fenylethery chemie   farmakokinetika   farmakologie   MeSH
• inhibitory enzymů chemie   farmakokinetika   farmakologie   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární modely MeSH
• synthasa oxidu dusnatého, typ I antagonisté a inhibitory   metabolismus   MeSH
• synthasa oxidu dusnatého, typ II antagonisté a inhibitory   metabolismus   MeSH
• synthasa oxidu dusnatého, typ III antagonisté a inhibitory   metabolismus   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminochinoliny MeSH
• fenylethery MeSH
• inhibitory enzymů MeSH
• phenyl ether MeSH Prohlížeč
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého MeSH