New azole antifungals with a fused triazinone scaffold

Montoir, David; Guillon, Rémi; Gazzola, Sophie; Ourliac‐Garnier, Isabelle; Soklou, Kossi Efouako; Tonnerre, Alain; Picot, Carine; Planchat, Aurélien; Pagniez, Fabrice; Pape, Patrice Le; Logé, Cédric

doi:10.1016/j.ejmech.2020.112082

Cited by 24 publications

(19 citation statements)

References 24 publications

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“…All experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication No. 80–23, revised 2011) and were approved by the Research and Ethics Committee of Tehran University of Medical Sciences (Code: IR.TUMS.VCR.REC.1397.912). − The mice were immunodepressed by IP injection of 100 mg/kg cyclophosphamide (Endoxan) in saline one day before inoculation. On day 1, the mice were infected (100 μL) with a suspension of fluconazole susceptible C.…”

Section: Methodsmentioning

confidence: 99%

“…Inspired by the promise shown by newly approved FLC analogous structures, a series of novel FLC derivatives bearing urea functionality were synthesized accordingly (Figure and Scheme ). Our experimental design was based on and taken from recent valuable studies in the field, including references , , , , and . Thus, all of the synthesis compounds were evaluated for their antifungal effects against 15 azole-sensitive ones: Candida albicans, non- albicans Candida , Aspergillus , and dermatophyte species by in vitro minimum inhibitory concentration (MIC) determination.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities

et al. 2021

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Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds 8b and 8c displayed broad-spectrum activity and superior in vitro antifungal capabilities compared to the standard drug FLC against sensitive and resistant Candida albicans (C. albicans). The highly active compounds 8b and 8c had potent antibiofilm properties against FLC-resistant C. albicans species. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure–activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally, in vivo results represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along with in vitro and in silico studies, demonstrating the therapeutic efficiency of compounds 8b and 8c as novel leads for candidiasis drug discovery.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities

et al. 2021

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“…Compound 26 of reported library exhibited significant in vitro antifungal activity against A. fumigatus , R. oryzae and M. circinelloides. Compound 26 displayed in vivo efficacy against two murine models of lethal systemic infections caused by C. albicans [ 104 ].…”

Section: Antifungal Agents Against Mucormycosismentioning

confidence: 99%

Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents

Hussain

Ahmed

Khan

et al. 2023

European Journal of Medicinal Chemistry

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“…Montoir et al [ 89 ] reported a novel class of azole antifungal compounds based on a pyrrolotriazinone scaffold. As a result, these compounds demonstrated fungicidal activity against pathogenic Candida species in vitro (fluconazole susceptible and fluconazole resistant) and were more active than voriconazole against two Candida albicans candidates .…”

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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New azole antifungals with a fused triazinone scaffold

Cited by 24 publications

References 24 publications

Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities

Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities

Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents

Novel 1, 2, 4-Triazoles as Antifungal Agents

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