Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Dascalu, Anca-Elena^1,2,3,4  Ghinet, Alina^1,2,4  Lipka, Emmanuelle^1,3  Furman, Christophe^1,5  Rigo, Benoit^1,2  Fayeulle, Antoine⁶  Billamboz, Muriel^1,2 

[1] Univ Lille, Facteurs Risque & Determinants Mol Malad Liees Vi, RID AGE, Inserm,CHU Lille,Inst Pasteur Lille,U1167, F-59000 Lille, France

[2] Ecole Hautes Etud Ingenieur HEI, Team Sustainable Chem, Hlth & Environm Dept, Lab Chim Durable & Sante, 13 Rue Toul, F-59046 Lille, France

[3] UFR Pharm, Lab Chim Analyt, BP 83, F-59006 Lille, France

[4] Alexandru Ioan Cuza Univ, Fac Chem, Bd Carol I 11, Iasi 700506, Romania

[5] Inst Chim Pharmaceut Albert Lespagnol, 3 Rue Prof Laguesse, F-59000 Lille, France

[6] Sorbonne Univ, Univ Technol Compiegne, ESCOM, EA TIMR 4297,Ctr Rech Royallieu, CS 60319, F-60203 Compiegne, France

关键词: Antifungal agents;    Biological screening;    Pyrrolidin-2-one;    Hydrazone;    Hydrazine;   

DOI  :  10.1016/j.bmcl.2020.127220

来源: Elsevier

【 摘 要 】

Twenty-eight 5-pyrrolidine-2-ones decorated by hydrazine or acyl hydrazones groups have been designed, synthesized and evaluated as antifungal agents on a panel of twelve fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. Half of the target compounds exhibited good to high antifungal activities on at least one strain with MIC50, lower than the control antifungal agent - hymexazol or ketoconazole. 5-Arylhydrazino-pyrrolidin-2-ones were found active and the -NH-NH- linker proved to be essential to maintain the antifungal potential. Compound 2a is a broad-spectrum antifungal, active on 60% of the tested strains. Replacing the hydrazine linker by an acylhydrazone one narrowed the spectrum of activity but pyroglutamylaryl hydrazones, mainly aromatic ones, exhibited good activity, adequate fungicide-like properties and were devoted of cytotoxicity.

【 授权许可】

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