Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design, synthesis and bioactive evaluation

Fang, Xianfu; Li, Di; Tangadanchu, Vijai Kumar Reddy; Goodla, Lavanya; Gao, Wei‐Wei; Zhou, Cheng‐He

doi:10.1016/j.bmcl.2017.10.020

Cited by 50 publications

(17 citation statements)

References 55 publications

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“…[22] Biochemical and pharmacological studies showedt hat the modification of the benzimidazole nucleus at the N1 and C2 positions coulde ffectively improve the bioactivity and attracted considerable attention. [23,24] All of these findings clearly demonstrated the great potential for benzimidazole compounds in treating microbial infections.…”

Section: Introductionmentioning

confidence: 94%

“…[17][18][19] Benzimidazole derivatives couldi nteract with DNA from different microbial strains or inhibitt he biosynthesis of essential ergosterol in the membrane of fungi and protozoa to exhibit antimicrobial activity. [23,24] All of these findings clearly demonstrated the great potential for benzimidazole compounds in treating microbial infections. [22] Biochemical and pharmacological studies showedt hat the modification of the benzimidazole nucleus at the N1 and C2 positions coulde ffectively improve the bioactivity and attracted considerable attention.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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A series of benzimidazole-quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2-fluorobenzyl derivative 5 b (ethyl 7-chloro-6-fluoro-1-[[1-[(2-fluorophenyl)methyl]benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep-2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV-DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug-resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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“…18,19 Some nonclinical hydroxyethyl azoles have also been developed with superior antibacterial or antifungal potencies. 20,21 These researches clearly demonstrated the enormous potentiality of hydroxyethyl azole in the antimicrobial aspect.…”

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confidence: 94%

Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of Enterococcus faecalis

Zhang

Tangadanchu

Cheng

et al. 2018

ACS Med. Chem. Lett.

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A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole 3f could effectively inhibit the growth of E. faecalis with minimal inhibitory concentration of 2 μg/mL. The active molecule 3f showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound 3f also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate 3f was membrane active against E. faecalis and could form 3f−DNA complex by intercalating into DNA of resistant E. faecalis, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative 3f with DNA gyrase enzyme through noncovalent interactions.

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“…albicans ATCC 90023 with MIC values of 0.02 and 0.008 mM, respectively. Compound 16e inhibited C. albicans rapidly, whereas compound 16a lacked fungicidal activity due to the lack of substituents on the phenyl ring ( ure 16 ) [ 99 ].…”

Section: 124 Triazole Scaffold For the Development Of Antifungal Agentsmentioning

confidence: 99%

Novel 1, 2, 4-Triazoles as Antifungal Agents

Kazeminejad

Marzi

Shiroudi

et al. 2022

BioMed Research International

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The development of innovative antifungal agents is essential. Some fungicidal agents are no longer effective due to resistance development, various side effects, and high toxicity. Therefore, the synthesis and development of some new antifungal agents are necessary. 1,2,4-Triazole is one of the most essential pharmacophore systems between five-membered heterocycles. The structure-activity relationship (SAR) of this nitrogen-containing heterocyclic compound showed potential antifungal activity. The 1,2,4-triazole core is present as the nucleus in a variety of antifungal drug categories. The most potent and broad activity of triazoles have confirmed them as pharmacologically significant moieties. The goal of this review is to highlight recent developments in the synthesis and SAR study of 1,2,4-triazole as a potential fungicidal compound. In this study, we provide the results of a biological activity evaluation using various structures and figures. Literature investigation showed that 1, 2, 4-triazole derivatives reveal the extensive span of antifungal activity. This review will assist researchers in the development of new potential antifungal drug candidates with high effectiveness and selectivity.

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Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design, synthesis and bioactive evaluation

Cited by 50 publications

References 55 publications

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of Enterococcus faecalis

Novel 1, 2, 4-Triazoles as Antifungal Agents

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