Recent insight into the biological activities and SAR of quinolone derivatives as multifunctional scaffold

Sharma, Vishal; Das, Rina; Mehta, Dinesh Kumar; Gupta, Sumeet; Venugopala, Katharigatta N.; Mailavaram, Raghuprasad; Nair, Anroop B.; Shakya, Ashok K.; Deb, Pran Kishore

doi:10.1016/j.bmc.2022.116674

Cited by 30 publications

(5 citation statements)

References 135 publications

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“…In this investigation, the docking score and H-bond interactions of synthesized derivatives were computed and shown as dotted green color lines. Out of all screened compounds, twelve derivatives were estimated to be having best binding a nity in terms of kcal/mol with common residues (ARG72, ARG78, ARG57, LYS32, SER49, LEU54, ILE94, ALA6, THR100, PHE31, MET16) and exhibited con rmed free energy of binding ranged from -4.5 to -8.6 kcal/mol, as shown in gures (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Compound 4f, 4h & 4k estimated best free energy of binding, -8.4, -8.6 & -8.5 kcal/mol into the binding pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands, as represented in gure 2, 5 & 8 and exhibited highest hydrogen bonding interaction with amino acids ARG57, ARG72 & ARG78.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

“…[3]. Based on a literature review, quinolones demonstrated several biological pro les in addition to their ability to ght bacteria like anti-in ammatory [4][5], anti-HCV [6], anti-cancer [7][8][9][10][11], antimalarial [12][13], anti-HIV [14][15], and antidepressant activities [16]. Many quinolone derivatives are used in clinics as antibacterial drugs, such as MCB3837, MCB3681, CBR-2092 (rifamycin-quinolone conjugate), and Ro-23-9424 (in phase II clinical study) to treat a variety of infections [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

Sharma,

Das,

Mehta

et al. 2024

Preprint

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A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using candida albicans (ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. The structure of synthesized derivatives was confirmed by IR, 1H NMR and Mass spectrometry techniques. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were found to be effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed potent antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds (4a–l) did not respond well against the Candida albicans fungal strain. The compound (4k) represents the high % inhibition against COX-II. The compounds (4f, 4h & 4k) exhibited the highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of -8.4, -8.6 & -8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, the quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.

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Section: Molecular Docking Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

Sharma,

Das,

Mehta

et al. 2024

Preprint

Self Cite

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“…Various research and review articles have been published on quinolones and their antibacterial, as well as other biological properties [49,50]. The previous review articles were focused either on antimicrobial drugs/molecules with different targets [51][52][53][54][55], or molecules effective against a specific target, such as protein synthesis [56,57], cell wall [58,59], and DNA gyrase [60][61][62][63]. Although many have covered the breadth needed as well as the importance of quinolones in drug discovery [64][65][66][67][68], we could not locate any reports which exclusively focus on the DNA gyrase inhibitory properties of quinolone and the detailed insights.…”

Section: Synthetic 4-quinolones Targeting Dna Gyrasementioning

confidence: 99%

DNA Gyrase as a Target for Quinolones

Spencer

Panda

2023

Biomedicines

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Bacterial DNA gyrase is a type II topoisomerase that can introduce negative supercoils to DNA substrates and is a clinically-relevant target for the development of new antibacterials. DNA gyrase is one of the primary targets of quinolones, broad-spectrum antibacterial agents and are used as a first-line drug for various types of infections. However, currently used quinolones are becoming less effective due to drug resistance. Common resistance comes in the form of mutation in enzyme targets, with this type being the most clinically relevant. Additional mechanisms, conducive to quinolone resistance, are arbitrated by chromosomal mutations and/or plasmid-gene uptake that can alter quinolone cellular concentration and interaction with the target, or affect drug metabolism. Significant synthetic strategies have been employed to modify the quinolone scaffold and/or develop novel quinolones to overcome the resistance problem. This review discusses the development of quinolone antibiotics targeting DNA gyrase to overcome bacterial resistance and reduce toxicity. Moreover, structural activity relationship (SAR) data included in this review could be useful for the development of future generations of quinolone antibiotics.

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“…These compounds are used, in particular, to treat a number of infections as they are broad-spectrum antibiotics, active against both Gram-positive and Gram-negative bacteria . However, depending on the nature and position of the substituents decorating this azaheteroaromatic system, biological properties such as antimalarial, antituberculosis, anti-HIV, or anticancer have also been demonstrated . As a result, quinolone derivatives have attracted considerable attention from synthetic chemists due to their wide range of potential applications.…”

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confidence: 99%

Atroposelective Construction of Axially Chiral 2-Aryl-Pyrroloquinolones

Khlifi,

Jbilou,

Leblais

et al. 2024

Org. Lett.

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A two-step protocol including an enantioselective organocatalyzed synthesis of pyrroloquinolines followed by an oxidation reaction allowed the formation of axially chiral 2-aryl-pyrroloquinolones. Thorough optimization of the experimental conditions for the second step allowed the oxygenation reaction to take place and ensured, in most cases, a central-to-axial chirality conversion with complete retention of the enantiomeric excess.

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Recent insight into the biological activities and SAR of quinolone derivatives as multifunctional scaffold

Cited by 30 publications

References 135 publications

Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

DNA Gyrase as a Target for Quinolones

Atroposelective Construction of Axially Chiral 2-Aryl-Pyrroloquinolones

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