Prenylated Trans -Cinnamic Esters and Ethers against Clinical Fusarium spp.: Repositioning of Natural Compounds in Antimicrobial Discovery

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-01, Vol.26 (3), p.658
• Main Authors: Oufensou, Safa, Casalini, Stefano, Balmas, Virgilio, Carta, Paola, Chtioui, Wiem, Dettori, Maria A, Fabbri, Davide, Migheli, Quirico, Delogu, Giovanna
• Format: Article
• Language: English
• Subjects: Acids; Alcohol; Amphotericin B; Amphotericin B - pharmacology; Anti-Infective Agents - pharmacology; Antifungal activity; Antifungal agents; Antifungal Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial agents; Bioavailability; Biological Products - pharmacology; Chains; Cinnamic acid; Coumaric acid; drug development; Drug dosages; Drug Repositioning - methods; Esters; Esters - pharmacology; Ethers; Ethers - pharmacology; Free radicals; Fungicides; Fusariosis - drug therapy; Fusariosis - microbiology; Fusarium; Fusarium - drug effects; Fusarium spp; Humans; Hydroxycinnamic acid; Lethal dose; Microbial Sensitivity Tests - methods; Minimum inhibitory concentration; mycoses; Onychomycosis; Onychomycosis - drug therapy; Onychomycosis - microbiology; p-Coumaric acid; Pesticides; phenolic inhibitors; Phenols; Terbinafine; Terbinafine - pharmacology
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26030658

Onychomycosis is a common nail infection mainly caused by species belonging to the , , and species complexes. The aim of this study was to evaluate the in vitro susceptibility of six representative strains of clinically relevant spp. toward a set of natural-occurring hydroxycinnamic acids and their derivatives with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. By introducing a prenylated chain at one of the hydroxy groups of -cinnamic acids - , ten prenylated derivatives (coded - ) were preliminarily investigated in solid Fusarium minimal medium (FMM). Minimal inhibitory concentration (MIC) and lethal dose 50 (LD ) values were then determined in liquid FMM for the most active selected antifungal -coumaric acid 3,3'-dimethyl allyl ester , in comparison with the conventional fungicides terbinafine (TRB) and amphotericin B (AmB), through the quantification of the fungal growth. Significant growth inhibition was observed for prenylated derivatives - , evidencing ester as the most active. This compound presented MIC and LD values (62-250 µM and 7.8-125 µM, respectively) comparable to those determined for TRB and AmB in the majority of the tested pathogenic strains. The position and size of the prenylated chain and the presence of a free phenol OH group appear crucial for the antifungal activity. This work represents the first report on the activity of prenylated cinnamic esters and ethers against clinical spp. and opens new avenues in the development of alternative antifungal compounds based on a drug repositioning strategy.