Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents

Xu, Yuanyuan; Qian, Anran; Cao, Xufeng; Ling, Chenyu; Cao, Yongbing; Wang, Rui-Lian; Li, Yi-Su; Yang, Yushe

doi:10.1016/j.cclet.2016.01.040

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…Xu et al [ 100 ] described a series of novel triazole derivatives having γ -lactam that were screened for antifungal activity against six pathogenic fungi in vitro . Furthermore, the pyridyl- and phenyl-substituted compounds 17d and 17e showed moderate antimicrobial activity against Cryptococcus neoformans and Candida spp.…”

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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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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“…Analysing structural properties of the active compounds, in particular comparing the isocoumarin and phtalide derivatives but also isocoumarins with and without directly attached azoles, it seems that activity might be related to the electrophilicity of the lactone carbonyl. Therefore we studied susceptibilities of active compounds 2a and 3b towards nucleophilic species 36 such as hydrazine and 2-phenylethylamine (Scheme 4). Both compounds underwent ring opening reaction under mild conditions at room temperature.…”

Section: Antifungal Activity and Cytotoxicitymentioning

confidence: 99%

Synthesis and biological profiling of novel isocoumarin derivatives and related compounds

Simić

Erić

Borić³

et al. 2021

JSCS

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In continuation of our study of substituted isocoumarins a series of novel 3-azolyl isocoumarin and their thio derivatives including related lactone compounds was prepared and biologically profiled against C. albicans showing, in general, moderate activity with MIC values in range of 4-60 mg mL?1. Additional characterization of selected compounds was carried out by exploring their activity on CYP3A4 and CYP2D6 enzymes whilst experiments on mutagenicity were performed by AMES test. The representative isocoumarins 3b, 4a and 4b showed less inhibitory activity on CYP enzymes compared to the reference inhibitors, ketoconazole and quinidine. Compound 4a showed a higher mutagenic potential than the other two compounds. Further characterization included cytotoxicity profiling against normal MRC5 cells.

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“…Albaconazole (UR-9825), developed by Palau Pharma S.A., is a novel triazole antifungal agent with broad-spectrum activity, good pharmacokinetics, and excellent oral bioavailability. − Albaconazole had been successfully assayed in several clinical trials, with indications including Candida vulvovaginitis, tinea pedis, and onychomycosis. − There has been extremely slow progress in the Phase III clinical studies of albaconazole, and no data have been disclosed to date, making it reasonable to presume that albaconazole may be a failure due to its strong CYP3A4 inhibition or other safety concerns. Despite a series of structural optimizations based on albaconazole, the problem of CYP3A4 inhibition has not been overcome. − …”

Section: Introductionmentioning

confidence: 99%

Discovery of a Novel Potent Tetrazole Antifungal Candidate with High Selectivity and Broad Spectrum

Ni,

Hao,

Ding

et al. 2024

J. Med. Chem.

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Thirty-one novel albaconazole derivatives were designed and synthesized based on our previous work. All compounds exhibited potent in vitro antifungal activities against seven pathogenic fungi. Among them, tetrazole compound D2 was the most potent antifungal with MIC values of <0.008, <0.008, and 2 μg/mL against Candida albicans, Cryptococcus neoformans, and Aspergillus f umigatus, respectively, the three most common and critical priority pathogenic fungi. In addition, compound D2 also exhibited potent activity against fluconazole-resistant C. auris isolates. Notably, compound D2 showed a lower inhibitory activity in vitro against human CYP450 enzymes as well as a lower inhibitory effect on the hERG K + channel, indicating a low risk of drug−drug interactions and QT prolongation. Moreover, with improved pharmacokinetic profiles, compound D2 showed better in vivo efficacy than albaconazole at reducing fungal burden and extending the survival of C. albicans-infected mice. Taken together, compound D2 will be further investigated as a promising candidate.

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Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents

Cited by 9 publications

References 14 publications

Novel 1, 2, 4-Triazoles as Antifungal Agents

Novel 1, 2, 4-Triazoles as Antifungal Agents

Synthesis and biological profiling of novel isocoumarin derivatives and related compounds

Discovery of a Novel Potent Tetrazole Antifungal Candidate with High Selectivity and Broad Spectrum

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