Series Of 8-hydroxyquinoline Research Articles

Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase.

A series of 8-hydroxy quinolines were identified as potent inhibitors of catechol O-methyltransferase (COMT) with selectivity for the membrane-bound form of the enzyme. Small substituents at the 7-position of the quinoline were found to increase metabolic stability without sacrificing potency. Compounds with good pharmacokinetics and brain penetration were identified and demonstrated in vivo modulation of dopamine metabolites in the brain. An X-ray cocrystal structure of compound 21 in the S-COMT active site shows chelation of the active site magnesium similar to catechol-based inhibitors. These compounds should prove useful for treatment of many neurological and psychiatric conditions associated with compromised cortical dopamine signaling.

Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa , Caco-2 and MCF7 . The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e . The ethyl ester was converted into corresponding carbohydrazide 3a-e . Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl)-5-(substituted phenyl)-1,3,4-oxadiazole 4a-e . The 2-(chloromethyl)-5-(substituted phenyl)-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e . Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC 50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

Design, Synthesis and Screening of Newer-8-Hydroxy Quinoline Derivatives as Novel Anti Tubercular Agents

A series of 8-hydroxyquinolines are synthesized and their Antitubercular, antifungal, and antibacterial activities are tested. Quinolines are found to possess antibacterial, antifungal, immunosuppressive, analgesic, vasorelaxing, Antiplasmodial, anticancer and PDE4 inhibitory activities. Aryloxypropanolamines were reported to be associated with β-adrenergic blocking, CNS depressant and hypotensive activities. In view of the potential nature of these moieties it was considered worthwhile to study the effects of two pharmacophoric moieties such as quinoline and propanolamines/amino ethane in a single molecule. In the present study the synthesis, antitubercular, antifungal, and antibacterial activities and structure activity relationship of aryloxypropanolamine substituted 8-hydroxy quinolines are reported. The compounds were characterized by IR, H-NMR, spectral and Elemental analysis. DOI: http://dx.doi.org/10.3126/ijasbt.v2i3.11100Int J Appl Sci Biotechnol, Vol. 2(3): 342-358

A MurF Inhibitor That Disrupts Cell Wall Biosynthesis in Escherichia coli

MurF is an essential enzyme of bacterial cell wall biosynthesis. Few MurF inhibitors have been reported, and none have displayed measurable antibacterial activity. Through the use of a MurF binding assay, a series of 8-hydroxyquinolines that bound to the Escherichia coli enzyme and inhibited its activity was identified. To derive additional chemotypes lacking 8-hydroxyquinoline, a known chelating moiety, a pharmacophore model was constructed from the series and used to select compounds for testing in the MurF binding and enzymatic inhibition assays. Whereas the original diverse library yielded 0.01% positive compounds in the binding assay, of which 6% inhibited MurF enzymatic activity, the pharmacophore-selected set yielded 14% positive compounds, of which 37% inhibited the enzyme, suggesting that the model enriched for compounds with affinity to MurF. A 4-phenylpiperidine (4-PP) derivative identified by this process displayed antibacterial activity (MIC of 8 microg/ml against permeable E. coli) including cell lysis and a 5-log(10)-unit decrease in CFU. Importantly, treatment of E. coli with 4-PP resulted in a 15-fold increase in the amount of the MurF UDP-MurNAc-tripeptide substrate, and a 50% reduction in the amount of the MurF UDP-MurNAc-pentapeptide product, consistent with inhibition of the MurF enzyme within bacterial cells. Thus, 4-PP is the first reported inhibitor of the MurF enzyme that may contribute to antibacterial activity by interfering with cell wall biosynthesis.

Structure-based design, synthesis, and SAR evaluation of a new series of 8-hydroxyquinolines as HIF-1α prolyl hydroxylase inhibitors

A new series of potent 8-hydroxyquinolines was designed based on the newly resolved X-ray crystal structure of EGLN-1. Both alkyl and aryl 8-hydroxyquinoline-7-carboxyamides were good HIF-1α prolyl hydroxylase (EGLN) inhibitors. In subsequent VEGF induction assays, these exhibited potent VEGF activity. In addition, this class of compounds did show the ability to stabilize HIF-1α.

Inter-ring Long-range Spin-Spin Proton Coupling in some 8-Hydroxyquinoline Derivatives

A study of the 1 H NMR spectra of a series of 8-hydroxyquinolines has been carried out using the 2D-COSYLR method and inter-ring proton spin-spin coupling constants 4 J , 5 J , 6 J and 7 J have been detected; it has been established that the π- mechanism for transmission of spin–spin coupling predominates and in the case of the planar zig-zag arrangement this results in unexpected annulment of 6 J 2,7 and 6 J 3,6 .