Honokiol, magnolol and its monoacetyl derivative show strong anti-fungal effect on Fusarium isolates of clinical relevance.

Safa Oufensou,Giovanna Delogu,Barbara Scherm,Ismael Malbrán,Davide Fabbri,Quirico Migheli,Giovanna Pani,Maria Antonietta Dettori,Virgilio Balmas,Paola Carta,Petr Karlovsky

doi:10.1371/journal.pone.0221249

Abstract

The antifungal activity of magnolol and honokiol, two naturally occurring hydroxylated biphenyls, and of their synthetic derivatives was evaluated on a collection of representative isolates of Fusarium oxysporum, F. solani and F. verticillioides of clinical and ecological concern. The tested compounds were proposed as a ‘natural’ alternative to conventional fungicides, even though a larger range of concentrations (5–400 μg/ml) was applied. The activity of magnolol and honokiol was compared with that of terbinafine (0.1–10 μg/ml), and fluconazole (1–50 μg/ml), two fungicides widely used in treating fungal infections on humans. Magnolol showed similar fungicidal activity compared to fluconazole, whereas honokiol was more effective in inhibiting mycelium growth compared to this fungicide on all tested clinical Fusarium spp. isolates. Compared to terbinafine, honokiol showed similar antifungal activity when tested on clinical F. solani isolates, whereas magnolol was less effective at all selected concentrations (5–400 μg/ml). The different position of the phenol-OH group, as well as its protection, explain different in vitro activities between magnolol, honokiol, and their derivatives. Furthermore, magnolol showed mycelium dry weight reduction at a concentration of 0.5 mM when tested on a set of agricultural isolates of Fusaria, leading to complete inhibition of some of them. Magnolol and honokiol are proposed as efficient and safe candidates for treating clinically relevant Fusaria.

Highlights

Natural occurring polyphenols are a great source of biologically active compounds beneficial to human and animal health [1]
Except for F. crookwellense 6, F. crookwellense 406, F. oxysporum 127, F. oxysporum 222, F. oxysporum 516, F. solani 95, and F. solani 100, the remaining 25 Fusarium isolates underwent a mycelium dry weight reduction greater than 50% when exposed to magnolol 1 at 0.5 mM (Table 3)
Magnolol 1 showed better or similar inhibitory activity than fluconazole at 5 μg/ml, whereas honokiol 2 showed a higher inhibition of mycelium growth compared to the conventional fungicide for all clinical Fusarium species complexes (Figs B-D in Supporting Information)

Summary

Introduction

Natural occurring polyphenols are a great source of biologically active compounds beneficial to human and animal health [1]. The biological activity of magnolol 1 and honokiol 2 is likely to depend on the hydroxyl group located at the biphenyl moiety and the allyl chain in para (magnolol 1 and honokiol 2) and in ortho (honokiol 2) position to the phenol-OH group, which adds further features to these molecules, such as anti-oxidative, anti-proliferative, anti-fungal, anti-tumoral, anti-HIV and neuroprotective activities [3, 7,8,9,10] This wide array of positive properties makes the two molecules potential candidates in the search for new drugs effective at treating various inflammatory diseases, such as osteoarthritis or acne, and for prophylaxis of biofilm-forming streptococci causing caries [11]. This is the first time that magnolol 1 and honokiol 2 are assayed over a collection of Fusarium spp. relevant to both plant and human health

Material and methods

Results

Discussion