Chemistry and Mechanism of Action of the Quinolone Antibacterials

Brighty, Katherine E.; Gootz, Thomas D.

doi:10.1016/b978-012059517-4/50003-9

Cited by 59 publications

(77 citation statements)

References 222 publications

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“…As previously reported [23], high melting points, generally above 200 o C, indicate that the crystal forms of the compounds are very stable, thus contributing to lower water solubility of (fluoro)quinolones. The lower melting points observed for 5d, 6d and 5e (not higher than 200 o C) in comparison with those of other corresponding derivatives and leading compounds and in this respect, their higher water solubility, are in agreement with these observations.…”

Section: Solubilitymentioning

confidence: 68%

“…In addition, substitutions and myriad modifications in the quinolone core, specifically at position C-7, may change the primary target. Namely, as Brighty and Gootz pointed out, if CIPRO, TROVA, gemifloxacn (GEMI) and NOR select first a parC mutation, the primary target of MOXI and gatifloxacin (GATI) is gyrA [23].…”

Section: Antibacterial Screeningmentioning

confidence: 99%

“…At high pH values, amine group is in the free base form, while the carboxyl group exists as a carboxylate anion, providing the overall molecule negative charge. Therefore, the (fluoro)quinolones tend to be more soluble in water at acidic and/or basic pH [23].…”

Section: Solubilitymentioning

confidence: 99%

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Synthesis, physicochemical characterization and antibacterial activity of novel (benzoylamino)methyl derivatives of quinolones

Breznica-Selmani

Mladenovska

Dräger

et al. 2016

Maced. J. Chem. Chem. Eng.

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Herein we report the synthesis of different derivatives of (fluoro)quinolones norfloxacin, ciprofloxacin and pipemidic acid, by incorporating (benzoylamino)methyl on the free nitrogen of the pyperazinyl moiety. The compounds were structurally characterized by 1D and 2D NMR, FTIR and highresolution mass spectroscopy. In addition, their physicochemical properties were a matter of interest to be correlated with their structure and antimicrobial activity in vitro. Their antimicrobial activities were screened against Gram-positive, Gram-negative bacteria and C. albicans. Higher distribution coefficients and consequently lower water solubility were determined for all synthesized compounds than the ones of the corresponding leading compounds. Inconsequential correlations between the lipophilicity of the compounds and MIC were observed, suggesting that passive diffusion is not the only mechanism for their penetration into bacterial cells. Further studies are needed to determine how substitutions in the (fluoro)quinolone moiety affect the primary target(s), substrate behavior in respect to bacterial transporters and overall bioavailability.Keywords: (benzoylamino)methyl; quinolones; structure; physicochemical properties; antimicrobial activity СИНТЕЗА, ФИЗИЧКОХЕМИСКА КАРАКТЕРИЗАЦИЈА И АНТИБАКТЕРИСКА АКТИВНОСТ НА НОВИ (БЕНЗОИЛАМИНО)МЕТИЛНИ ДЕРИВАТИ НА ХИНОЛОНИВо трудот е прикажана синтеза на различни деривати на (флуоро)хинолони со инкорпорирање на (бензоиламино)метилна група на слободниот азот од пиперазинскиот фрагмент кај норфлоксацинот, ципрофлоксацинот и пипемидинската киселина како водечки соединенија. Синтетизираните соединенија беа структурно карактеризирани со помош на 1D и 2D NMR, FTIR и масена спектрометрија со висока резолуција. Дополнително беа определени физичкохемиските особини на новосинтетизираните соединенија и корелирани со нивната структура и антимикро- 179-197 (2016) 180 бната активност in vitro. Антимикробната активност на новите соединенија беше испитувана на Gram-позитивни и Gram-негативни бактерии и на C. albicans. Сите новосинтетизирани соеди-ненија покажаа повисок коефициент на распределба и соодветно пониска растворливост во вода во однос на водечките соединенија. Корелациите меѓу липофилноста на синтетизираните соединенија и минималната инхибиторна концентрација (MIC) не беа статистички значајни, што укажува на тоа дека пасивната дифузија не е единствениот механизам со кој тие пенетрираат во бактериските клетки. Потребни се понатамошни истражувања за да се испита како супституциите во (флуоро)хинолонското јадро влијаат врз примарната цел(и), супстратното однесување во однос на бактериските транспортери и севкупната биорасположливост.

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Section: Solubilitymentioning

confidence: 68%

Section: Antibacterial Screeningmentioning

confidence: 99%

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Synthesis, physicochemical characterization and antibacterial activity of novel (benzoylamino)methyl derivatives of quinolones

Breznica-Selmani

Mladenovska

Dräger

et al. 2016

Maced. J. Chem. Chem. Eng.

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“…Their large antibacterial spectrum includes anaerobes, Chlamydia and Mycoplasma. (Brighty & Gootz, 2000) Quinolones: Synthesis and Antibacterial Activity The four generations have the following common aspects: an identical mechanism of action by inhibition the A subunit of DNA-gyrasa, an exclusively chromosomal bacteria resistance and some similar bacteria effects: photo toxicity, neurotoxicity, cartilage toxicity. Until now a large number of antibacterial substances belonging to the above mentioned class have been used in medicine.…”

Section: Introductionmentioning

confidence: 99%

Quinolones: Synthesis and Antibacterial Activity

Pintilie¹

2012

Antimicrobial Agents

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“…These ITQs target bacterial replication and are potent inhibitors of both DNA gyrase and topoisomerase IV (5). A lead ITQ compound, ACH-702, has demonstrated potent antibacterial activity against a number of medically relevant bacteria, including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) (21,28,31).…”

mentioning

confidence: 99%

In Vitro Activity of a New Isothiazoloquinolone, ACH-702, against Mycobacterium tuberculosis and Other Mycobacteria

Molina-Torres

Ocampo‐Candiani

Rendón

et al. 2010

Antimicrob Agents Chemother

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In this work, we describe the activity of ACH-702 against clinical isolates of Mycobacterium tuberculosis and six different nontuberculous mycobacteria. The MIC 50 and MIC 90 of both susceptible and drug-resistant M. tuberculosis strains tested were 0.0625 and 0.125 g/ml, respectively. The MIC 50 and MIC 90 values for Mycobacterium fortuitum isolates were 0.0625 g/ml in both cases; Mycobacterium avium complex isolates showed MIC 50 and MIC 90 values of 0.25 and 4 g/ml, respectively.

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Chemistry and Mechanism of Action of the Quinolone Antibacterials

Cited by 59 publications

References 222 publications

Synthesis, physicochemical characterization and antibacterial activity of novel (benzoylamino)methyl derivatives of quinolones

Synthesis, physicochemical characterization and antibacterial activity of novel (benzoylamino)methyl derivatives of quinolones

Quinolones: Synthesis and Antibacterial Activity

In Vitro Activity of a New Isothiazoloquinolone, ACH-702, against Mycobacterium tuberculosis and Other Mycobacteria

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