Search Results (6)

The first examples of metallasilsesquioxane complexes, including ligands of the 8-hydroxyquinoline family 1–9, were synthesized, and their structures were established by single crystal X-ray diffraction using synchrotron radiation. Compounds 1–9 tend to form a type of sandwich-like cage of Cu₄M₂ nuclearity (M = Li, Na, K). Each complex includes two cisoid pentameric silsesquioxane ligands and two 8-hydroxyquinoline ligands. The latter coordinates the copper ions and corresponding alkaline metal ions (via the deprotonated oxygen site). A characteristic (size) of the alkaline metal ion and a variation of characteristics of nitrogen ligands (8-hydroxyquinoline vs. 5-chloro-8-hydroxyquinoline vs. 5,7-dibromo-8-hydroxyquinoline vs. 5,7-diiodo-8-hydroxyquinoline) are highly influential for the formation of the supramolecular structure of the complexes 3a, 5, and 7–9. The Cu₆Na₂-based compound 2 exhibits high catalytic activity towards the oxidation of (i) hydrocarbons by H₂O₂ activated with HNO₃, and (ii) alcohols by tert-butyl hydroperoxide. Studies of kinetics and their selectivity has led us to conclude that it is the hydroxyl radicals that play a crucial role in this process. Full article

The synthesis of alkyl 2-(4-hydroxyquinolin-2-yl) acetates and 1-phenyl-4-(phenylamino)pyridine-2,6(1H,3H)-dione was optimised. Starting from 4-hydroxyquinolines (4HQs), aminomethylation was carried out via the modified Mannich reaction (mMr) applying formaldehyde and piperidine, but a second paraformaldehyde molecule was incorporated into the Mannich product. The reaction also afforded the formation of bisquinoline derivatives. A new 1H-azeto [1,2-a]quinoline derivative was synthesised in two different ways; namely starting from the aminomethylated product or from the ester-hydrolysed 4HQ. When the aldehyde component was replaced with aromatic aldehydes, Knoevenagel condensation took place affording the formation of the corresponding benzylidene derivatives, with the concomitant generation of bisquinolines. The reactivity of salicylaldehyde and hydroxynaphthaldehydes was tested; under these conditions, partially saturated lactones were formed through spontaneous ring closure. The activity of the derivatives was assessed using doxorubicin-sensitive and -resistant colon adenocarcinoma cell lines and normal human fibroblasts. Some derivatives possessed selective toxicity towards resistant cancer cells compared to doxorubicin-sensitive cancer cells and normal fibroblasts. Cytotoxic activity of the benzylidene derivatives and the corresponding Hammett–Brown substituent were correlated. Full article

The opportunistic pathogen Pseudomonas aeruginosa employs quorum sensing to govern the production of many virulence factors. Interference with quorum sensing signaling has therefore been put forward as an attractive approach to disarm this pathogen. Here, we analyzed the quorum quenching properties of natural and engineered (2-alkyl-)3-hydroxy-4(1H)-quinolone 2,4-dioxygenases (HQDs) that inactivate the P. aeruginosa signal molecule PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4(1H)-quinolone). When added exogenously to P. aeruginosa cultures, all HQDs tested significantly reduced the levels of PQS and other alkylquinolone-type secondary metabolites deriving from the biosynthetic pathway, such as the respiratory inhibitor 2-heptyl-4-hydroxyquinoline N-oxide. HQDs from Nocardia farcinica and Streptomyces bingchenggensis, which combine low K_M values for PQS with thermal stability and resilience in the presence of P. aeruginosa exoproducts, respectively, attenuated production of the virulence factors pyocyanin and pyoverdine. A delay in mortality was observed when Galleria mellonella larvae were infected with P. aeruginosa suspensions treated with the S. bingchenggensis HQD or with inhibitors of alkylquinolone biosynthesis. Our data indicate that quenching of PQS signaling has potential as an anti-virulence strategy; however, an efficient anti-virulence therapy against P. aeruginosa likely requires a combination of agents addressing multiple targets. Full article

The ethylation of aryl alcohols by an ethyl moiety of boron trifluoride etherate is described. The reaction proceeded cleanly and afforded good yields of the corresponding aryl ethyl ethers. It tolerated the presence of functional groups such as aryl, alkyl, halogens, nitro, nitrile, and amino. However, the presence of amino or nitro groups ortho to a hydroxyl group of an aryl compound drastically reduced the yields of the anticipated products due to the chelation of the aforementioned functional groups with boron trifluoride etherate. A nitrogen atom in the aromatic ring system, as exemplified by hydroxypyridine and 8-hydroxyquinoline, completely inhibited the reaction. Resorcinol, hydroquinone, and aryl alcohols with aldehyde functions decomposed under the reaction conditions. Full article

Four 2-alkyl-4-hydroxyquinoline derivatives (1–4) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC₅₀ value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans. Full article

The starting materials, 2-amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-pyran0[3,2-hlquinoline 1 and ethyl-2-amino-4-(3,4,5-trimethoxyphenyl)-4H-pyrano [3,2-hlquinolin-3-carboxylate 2 were synthesised from 8-hydroxyquinoline and a-cyano-3,4,5-trimethoxycinnamonitrileand/or ethyl-a-cyano-3,4,5-trimethoxy-cinnamatre respectively. In order to construct a third heterocyclic ring 1 and 2were condensed with ethyl bromoacetate, formarnide, carbon disulfide to afford pyrrolo-, pyrimido- and thiazinopyranoquinolines 3-6respectively. The S-alkylated products 7 and 8 were obtained by the effect of chloroacetonitrile and/or ethyl chloroacetate on thiazinopyranoquinoline derivative 6. The attempt of cyanomethylation of the amino functional group of 1 to yield 10 with chloroacetonitrile in AcOHIAcONa failed and instead, pyridopyranoquinoline derivative 9 was obtained which is visualized to occur via cyclization of the initially formed acetylarnino derivative by nucleophilic attack on the cyano group. Acetylation of 1 and 2 with acetic anhydride afforded the mono- and di-acetyl derivatives 11a and 11b respectively. A plausible explanation to form the mono-derivative with 1 and the di-derivative with 2 is the higher deactivating effect of the cyano function over that of the carboxyethyl group. Furoylation of 1 and 2 was achieved by furoyl chloride to give 12a and 12b respectively. The structural features of pyranoquinoline 2 were inferred from its microanalysis and spectral data such as IR,¹H-NMR and MS as well as its chemical reactions, as a bifunctional compound with carbon nucleophiles namely, phenyl isothiocyanate and nitrogen nucleophilic species namely, p-toluidine, benzylamine, aniline and hydrazine hydrate to give pyrimidopyranoquinoline derivative 13, carboxamides 14a-c and carboxyhydrazide 15 respectively. When the hydrazide 15 was treated with carbon disulfide inpresence of KOH, it afforded the potassium salt 16 which was submitted to react with hydrazine hydrate at room temperature to give 17. The hydrazido group of 15was utilized to construct heterocyclic moieties attached to postion-3 of the pyranoquinoline structure. Thus, the reaction of the carboxyhydrazide15 with phenyl isothiocyanate, acetylacetone, and benzoylacetone resulted in the formation of 18, 19a and 19b respectively. Ethyl carbazate as a typical mesophile reacted with 2 to afford a fused tetracyclic product triazepinopyranoquinoline 20 via cyclization of the initially formed hydrazide. Among sixteen compounds screened against E. coli and S. aureus respectively,compounds 2 and 14c show a high order of antibacterial activity against both bacteria. 12b is strongly potent against Staphylococcus aureus. Full article