Quantitative structure-activity relations for 5-substituted 8-hydroxyquinolines as inhibitors of dental plaque

Warner, Victor D.; Musto, Joseph D.; Sane, Jayant N.; Kim, Ki Hwan; Grunewald, Gary L.

doi:10.1021/jm00211a019

Cited by 16 publications

(14 citation statements)

References 5 publications

(8 reference statements)

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“…As the pH rises, it dissociates to OO Ϫ , giving another electronic resonance to the molecule, which causes a change in absorbance. The pHtitration curve obtained showed that half of the OOH groups are dissociated at pH 6.3, corresponding to the pK a ; this was in agreement with the value of 5.97 obtained from previous chemical studies with a different solvent (50). The pH-dependent absorption intensity of NIT was maximal at pH 8.4 ( Fig.…”

Section: Spectrophotometric Assays (I) Effects Of Ph On Nit Absorptionsupporting

confidence: 90%

Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains

Pelletier

Prognon

Bourlioux

1995

Antimicrob Agents Chemother

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The antibacterial activity of nitroxoline (NIT), an antibiotic used in the treatment of acute or recurrent urinary tract infections caused by Escherichia coli, is decreased in the presence of Mg 2؉ and Mn 2؉ but not Ca 2؉ . In order to elucidate the interaction between this drug and the divalent cations, spectrophotometric studies based on the natural absorption of the nitroxoline moiety were conducted. In the presence of the divalent metal ions, a shift in the NIT A 448 suggested the formation of drug-ion complexes, for which the stability followed the order Mn 2؉ > Mg 2؉ > Ca 2؉. A clear correlation was found between the chelating property and antibacterial activity of NIT; both were pH dependent. A convenient colorimetric method for the determination of NIT uptake by bacterial cells was also developed. Uptake was energy independent and showed biphasic kinetics: a rapid association with cells and then a slower increase in cell-associated NIT which reached a plateau. NIT uptake was reduced in the presence of magnesium. The implications of metal ion complexation and pH on the clinical efficacy of NIT are discussed.Nitroxoline (NIT), or 5-nitro-8-hydroxyquinoline, is an antibiotic which does not belong to any known antimicrobial class. This drug is used in France in the treatment of acute or recurrent urinary tract infections (UTIs) (14, 26) since it shows bacteriostatic activity against Escherichia coli strains frequently encountered in UTIs. On the other hand, the pharmacokinetics of NIT in plasma and urine are well established (4). NIT also possesses fungistatic activity (11) and bactericidal properties against Mycoplasma spp. (7).Recent studies have shown an inhibition of adherence of uropathogenic E. coli to uroepithelial cells (27) and urinary catheters (8) at sub-MICs of NIT. In order to explain this activity Bourlioux et al. (9) proposed that NIT promotes a disorganization of the bacterial outer membrane resulting from the chelation by NIT of the divalent ions Mg 2ϩ and Ca 2ϩ . The same investigators observed a decrease in the antibacterial activity of NIT on E. coli in the presence of some divalent metal ions (9). It is interesting to note that 8-hydroxyquinoline (oxine) and its derivatives have been reported to complex with metal ions (23, 37).To acquire further information on the mechanism of action of NIT and the behavior of the molecule toward the bacterial envelope, the interaction between NIT and some divalent metal ions was spectrophotometrically examined by using the absorption properties of the molecule in the visible region. In addition, microbiological investigations were carried out to determine the role of these ions and the pH in the antibacterial activity of NIT. The uptake of NIT by E. coli was also studied. MATERIALS AND METHODSBacterial strains and culture conditions. Three strains of E. coli were studied. Strains J96 and AL46 were isolated from patients with UTIs. J96 is a standard strain, frequently used in bacterial adherence assays, expressing type 1 and P fimbriae (24); the AL...

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Section: Spectrophotometric Assays (I) Effects Of Ph On Nit Absorptionsupporting

confidence: 90%

Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains

Pelletier

Prognon

Bourlioux

1995

Antimicrob Agents Chemother

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“…Antimicrobial effects of 8HQ and its derivatives encompassing antibacterial,102–104 antimalarial,105–107 antiviral,108 antitubercular,109 and antidental plaque activities110,111 have been previously reported.…”

Section: Introductionmentioning

confidence: 94%

“…CQ and 5,7-dichloro-8HQ exerted a bactericidal effect at 0.05% concentration on S. mutans (cariogenic) and A. viscosus (periodontogenic), whereas 8HQ sulfate showed a bacteriostatic effect against both pathogens at a higher (0.3%) concentration 111. It was demonstrated that halogenated 8HQs were more potent dental plaque inhibitors 110,111. The low water solubility is a limitation in using these bioactive compounds via an aqueous vehicle such as mouth rinse 111.…”

Section: Introductionmentioning

confidence: 99%

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8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications

Prachayasittikul¹,

Prachayasittikul²,

Ruchirawat³

et al. 2013

DDDT

354

276

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Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships.

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“…Only some QSAR or RP-TLC studies of variously substituted quinolines or substituted 4(1H)-quinolinones have been reported [40,41]. A number of chromatographic studies of diazine hydrophobicity were found.…”

Section: Lipophilicitymentioning

confidence: 99%

RP-HPLC determination of lipophilicity in series of quinoline derivatives

et al. 2009

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Abstract:In the present paper we describe results on the synthesis and lipophilicity determination of a series of biologically active compounds based on their heterocyclic structure. For synthesis of styrylquinoline-based compounds we applied microwave irradiation and solid phase techniques. The correlation between RP-HPLC retention parameter log k (the logarithm of retention factor k) and log P data calculated in various ways is discussed, as well as, the relationships between the lipophilicity and the chemical structure of the studied compounds.© Versita Warsaw and Springer-Verlag Berlin Heidelberg.

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Quantitative structure-activity relations for 5-substituted 8-hydroxyquinolines as inhibitors of dental plaque

Cited by 16 publications

References 5 publications

Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains

Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains

8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications

RP-HPLC determination of lipophilicity in series of quinoline derivatives

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