Sustainable synthesis and characterization of honokiol, magnolol derivatives and their anti-fungal effect on Fusarium isolates of clinical relevance

PAOLA CARTA; SAFA OUFENSOU; BARBARA SCHERM; GIOVANNA PANI; VIRGILIO BALMAS; DAVIDE FABBRI; M. A. DETTORI; ISMAEL MALBRÁN; QUIRICO MIGHELI; GIOVANNA DELOGU

Bressanone

Conferencia; Conferenza di Dipartimento 2019; 2019

Consiglio Nazionale delle Ricerche - Department of Chemical Sciences and Materials Technology

Fusarium spp. are common human pathogenic fungi implicated in invasive mycoses and infections. In humans, Fusarium spp., particularly F. verticillioides, F. solani and F. oxysporum, are frequently reported as the cause of several dermatological affections such as onychomycoses and paronychia, but they may also induce keratitis episodes, mainly as a consequence of contaminated lens solutions. In our previous studies, devoted to the search of effective sustainable fungicides in agriculture, we have observed antifungal activity of magnolol 1 and honokiol 2 against F. graminearum and F. culmorum in vitro and in silico. Magnolol 1 and honokiol 2 are two hydroxylated biphenyls representing the main components of the bark of Magnolia officinalis. These compounds have long been important substances in traditional chinese and Ayurvedic medicine due to their wide biological activities. Magnolol 1 manifested the highest anti-fungal activity among a wide range of natural occurring phenols and it is generally recognized as harmless for humans and animal as well as its isomer honokiol 2. Unfortunately, the poor aqueous solubility of these two hydroxylated biphenyls has hampered their broad clinical application. This study shows a synthetic strategy to improve the bioactivity of magnolol 1 and honokiol 2 by transformation of their hydroxyl groups in an ester group or in an acetal group with a glucosyl unit. The synthetic methodology presented followed diverse sustainable and practical approaches, including the use of green reaction media and alternative technologies such as microwave. Magnolol 1, honokiol 2 and their derivatives 3-8 were tested for their anti-fungal activity and specificity towards human and nosocomial isolates and their activity was compared with that of terbinafine and fluconazole, two conventional fungicides.