Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents

Zhao, Liyu; Tian, Linfeng; Sun, Nannan; Sun, Yin; Chen, Yixuan; Wang, Xinran; Zhao, Shizhen; X, Su; Cheng, Maosheng

doi:10.1016/j.ejmech.2019.05.047

Cited by 36 publications

(22 citation statements)

References 19 publications

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“…These NSAIDs (FP, KP, NP) reacted with aminoacetophenone (12 ) by the amidation reaction and generated the corresponding intermediates ( 13-1, 2, 3 ). Subsequently, they were further converted into intermediates ( 14-1, 2, 3 ) by introducing the hydroxymethyl group . On this basis, they were further sulfonated with TsCl to produce key intermediates ( 15-1, 2, 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, they were further converted into intermediates (14-1, 2, 3) by introducing the hydroxymethyl group. 36 On this basis, they were further sulfonated with TsCl to produce key intermediates (15-1, 2, 3). Finally, these desired compounds (16a, b-1, 2, 3) were obtained via the substitution reaction of intermediates (15-1, 2, 3) and imidazole (triazole).…”

Section: Chemistrymentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of Dual-Target COX-2/CYP51 Inhibitors for the Treatment of Fungal Infectious Diseases

Liu

Fan

et al. 2022

J. Med. Chem.

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The design of novel dual-target (COX-2/CYP51) inhibitors was proposed in the study, and three series of compounds were constructed though the pathway of skeleton screening and combination; their molecular structures were synthesized and evaluated. Most of the compounds exhibited significant antifungal ability. Among them, potential compounds (10a-2, 16b-3) with excellent antifungal and anti-drug-resistant fungal ability (MIC50, 0.125–2.0 μg/mL) were selected for the subsequent mechanistic study. On the one hand, these compounds could block the ergosterol biosynthesis pathway by inhibiting CYP51 and influence the internal physiological function of fungal cells, which included the increase of the ROS level, the anomaly of ΔΨm, and the emergence of an apoptotic state. On the other hand, these compounds also effectively showed COX-2 inhibition ability, eliminated the inflammatory reaction of the infected region, and activated the body’s immune function. In summary, this study not only provided a novel antifungal drug design pathway but also discovered excellent target compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Dual-Target COX-2/CYP51 Inhibitors for the Treatment of Fungal Infectious Diseases

Liu

Fan

et al. 2022

J. Med. Chem.

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“…However, some problems remain, such as severe drug resistance, cytotoxicity. However, emergence of drug resistance, environmental hazards and other problems objectively indicate the urgent need for novel antifungal agents [2,9]. Nitrogen heterocycles are common structural motifs in compounds with antifungal activity [4].…”

Section: Introductionmentioning

confidence: 99%

“…are still the three main pathogens of fungal infections. Over the last few decades, the occurrence of systemic fungal infections has increased considerably in immunocompromised hosts, particularly patients who receive cancer chemotherapy or patients with AIDS and undergone organ transplantation [1][2][3]. Some research teams stated that Candida albicans (C. albicans) which caused severe mucosal infections with potentially fatal invasive infections was the most common fungus in these patients [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, only a restricted number of antifungal agents are formerly accessible to treat these life-threatening fungal infections [6]. Presently, clinical antifungal agents can be separated into four classes: Echinocandins (such as Micafungin and Caspofungin), antimetabolites (such as 5-fluorocytosine) polyenes (such as Nystatin and Amphotericin B) and azoles (such as Itraconazole and Fluconazole) [2,3].…”

Section: Introductionmentioning

confidence: 99%

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Antifungal Activity of Some Benzimidazole-Hydrazones

Osmaniye

Çevik

2019

Cumhuriyet Science Journal

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In the present work, 15 4-(1-(prop-2-in-1-yl)-1H-benzoimidazole-2-yl)-N'-(substitutedmethylene)benzohydrazide derivatives (4a-4o) were re-synthesized to evaluate their antifungal activity. Structure identification of synthesized compounds was elucidated by 1 H-NMR, 13 C-NMR, and HRMS spectroscopic methods. Inhibitory potential of the re-synthesized compounds was investigated against Candida supp. The compounds 4e and 4l showed significant anti fungal activity. Consistent with the activity studies, 4e was found to be potent derivative with its MIC50 value of (1.95 µg/mL) against Candida glabrata. And 4l was found to be potent derivative with its MIC50 value of (1.95 µg/mL) against Candida krusei.Özet. Mevcut çalışmada, 15 4-(1-(prop-2-in-1-il)-1H-benzimidazol-2-il)-N'-(sübstitüemetilen) benzohidrazit türevleri (4a-4o), antifungal aktivitelerini değerlendirmek üzere yeniden sentezlendi. Sentezlenen bileşiklerin yapı tanımlamaları 1 H-NMR, 13 C-NMR ve HRMS spektroskopik yöntemlerle açıklandı. Yeniden sentezlenen bileşiklerin antifungal etkinlikleri Candida türlerine karşı değerlendirildi. Bileşik 4e ve 4l önemli aktivite gösterdi. Aktivite çalışmaları ile uyumlu olarak, 4e bileşiği Candida glabrata'ya karşı 1.95 µg / mL MIC50 değeri ile güçlü bir türev olarak bulundu. Aynı zamanda 4l bileşiği Candida krusei'ye karşı 1.95 µg / mL MIC50 değeri ile güçlü bir türev olarak bulundu.

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Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation

Sui

Ansari

Zhou

2021

Chemistry An Asian Journal

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Substantial morbidity and mortality of fungal infections have aroused concerns all over the world, and common Candida spp. currently bring about severe systemic infections. A series of pyrimidinetrione-imidazole conjugates as potentially antifungal agents were developed. Bioassays manifested that 4fluobenzyl pyrimidinetrione imidazole 5 f exerted favorable inhibition towards C. albicans (MIC = 0.002 mM), being 6.5 folds more active than clinical antifungal drug fluconazole (MIC = 0.013 mM). Preliminary mechanism research indicated that compound 5 f could not only depolarize membrane potential but also permeabilize the membrane of C. albicans. Molecular docking was operated to simulate the interaction mode between molecule 5 f and CYP51. In addition, hybrid 5 f might form 5 f-DNA supramolecular complex via intercalating into DNA. The interference of membrane and DNA might contribute to its fungicidal capacity with no obvious tendency to induce the resistance against C. albicans. Conjugate 5 f endowed good blood compatibility as well as low cytotoxicity towards HeLa and HEK-293T cells.

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Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents

Cited by 36 publications

References 19 publications

Design, Synthesis, and Biological Evaluation of Dual-Target COX-2/CYP51 Inhibitors for the Treatment of Fungal Infectious Diseases

Design, Synthesis, and Biological Evaluation of Dual-Target COX-2/CYP51 Inhibitors for the Treatment of Fungal Infectious Diseases

Antifungal Activity of Some Benzimidazole-Hydrazones

Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation

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