Design, synthesis and antifungal activity of pterolactam-inspired amide Mannich bases
Anca-Elena Dascalu1, Alina Ghinet2, Emmanuelle Lipka3
1Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000 Lille, France; Laboratoire de Chimie Durable et Santé, Health & Environment Department, Team Sustainable Chemistry, Ecole des Hautes Etudes d'Ingénieur (HEI), Yncréa Hauts-de-France, 13 Rue de Toul, F-59046 Lille, France; UFR Pharmacie, Laboratoire de Chimie Analytique, BP 83, F-59006 Lille, France; 'Alexandru Ioan Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
Abstract:
Pterolactam (5-methoxypyrrolidin-2-one) is a heterocycle naturally occurring in plants. In an attempt to identify antifungal agents, a series of novel Mannich bases of amide derivated from Pterolactam have been designed, synthesized and their antifungal activities were evaluated on a panel of nine fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. A third of the target compounds exhibited good to high antifungal activities on at least one strain with EC50 lower than the control antifungal agent. N,N'-aminals derivated from Pterolactam proved to be good candidates for the development of biosourced fungicides, with compound 3o being the most broader-spectrum agent, active against five strains and devoted of any cytotoxicity.
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