Antifungal Activity of Griseofulvin Derivatives against Phytopathogenic Fungi in Vitro and in Vivo and Three-Dimensional Quantitative Structure–Activity Relationship Analysis

Abstract

With environmental pollution, residual hazards accumulate and severe drug resistance and many other problems appear; some highly toxic drugs have been banned, and antifungal agents are far from satisfactory. Natural products play an important role in the discovery and development of new pesticides. The natural product griseofulvin (1) has been known as an antifungal agent in the treatment of dermatomycoses for decades. In this study, a series of new griseofulvin derivatives were synthesized with good yields. Their structures were characterized by 1 H and 13 C nuclear magnetic resonance and highresolution mass spectrometry (electrospray ionization). The antifungal activities of griseofulvin analogues were first evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) in vitro. Of significance is that most of them showed excellent antifungal activities against C. gloeosporioides. The antifungal activities of the four best compounds (6a, 6c, 6e, and 6f) against C. gloeosporioides were further investigated in vivo using infected apples. The results suggested that compounds 6c, 6e, and 6f [half-maximal inhibitory concentration (IC 50 ) = 47.25 ± 1.46, 49.44 ± 1.50, and 53.63 ± 1.74 μg/mL, respectively] were better than thiophanate-methyl (IC 50 = 69.66 ± 6.07 μg/mL). Furthermore, comparative molecular field analysis was performed on the basis of the antifungal activity results of all 22 of the compounds against C. gloeosporioides in vitro. The three-dimensional coefficient contour plots revealed that the suitable bulky and electronegative acyl-substituted groups seem to be more favorable for increasing activity at the 4′ position of griseofulvin. The structure−activity relationships were also discussed. Griseofulvin derivatives can be used for the development of highly effective and safe agricultural fungicides.

Antibiotics from Extremophilic Micromycetes

“…Most of the new and known metabolites can be assigned to phenols and their derivatives and diphenyl esters (177)(178)(179)(180)(181)(182)(183)(184)(185)(186)(187)(188)(189). Many isolated metabolites were aromatic compounds, i.e., phenalenones (190)(191)(192)(193)(194)(195)(196)(197)(198), grisane metabolites (199)(200)(201), and azaphilones . Linear polyketides with various side chains and other polyketides (246)(247)(248)(249)(250)(251)(252)(253)(254)(255)(256)(257) were also obtained.…”

“…(179) Phenalenons are a fairly rare class of natural compounds [190]. When studying the marine fungus of the Penicillium genus [94], six undescribed phenalenon derivatives were isolated, i.e., peniciphenalenins A-F (190)(191)(192)(193)(194)(195) with no antibiotic activity ( Fig. 13).…”

Taxonomic Characterization, and Secondary Metabolite Analysis of Streptomyces triticiradicis sp. nov.: A Novel Actinomycete with Antifungal Activity

“…It is well known that plant pathogenic fungi can cause a tremendous loss of global agricultural production [1]. Despite synthetic fungicides being effective and playing an indispensable role against pathogenic fungi, the available antifungal agents are far from satisfactory as a result of several drawbacks, such as severe drug resistance, drug-related toxicity, and many other problems [2]. Therefore, novel 2 of 17 antifungal agents and antagonistic microorganisms are needed to effectively control the fungal diseases of agricultural crops.…”

Identification of antimicrobial metabolites produced by a potential biocontrol Actinomycete strain A217

“…However, pathogens have developed resistance to several of these chemicals (Bardas et al ). Furthermore, long‐term application of chemicals may lead to serious food and environmental pollution (Bai et al ; Nandinsuren et al ; Bai et al ). Therefore, recent studies have focussed on developing alternative control measures for plant fungal diseases.…”