Spectrum Of Antifungal Activity Research Articles

Design, Synthesis, and Antifungal Evaluation of Diverse Heterocyclic Hydrazide Derivatives as Potential Succinate Dehydrogenase Inhibitors.

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 μg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 μg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 μg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 μM, respectively, which were superior to that of boscalid (IC50 = 2.38 μM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.

Esporotricose felina: Sinais clínicos e prevenção em animais e humanos

Sporotrichosis is a mycosis caused by the fungus Sporothrix sp, which is found in plants, trees, and soil, associated with decomposing plant remains. The disease can affect various species, especially felines which, in turn, are the main transmitters of sporotrichosis to humans. Infection by Sporothrix sp. occurs through contact between injured skin and surfaces contaminated with the fungus, or scratching or biting by diseased animals. In addition to the skin manifestation, sporotrichosis can also occur in extracutaneous form, affecting multiple organs such as the lungs, lymph nodes, liver, spleen and kidneys. There is no preventive vaccine for the disease and it is treated with synthetic fungistatic agents with a broad spectrum of antifungal activity. Sporotrichosis is considered one of the most relevant mycoses in veterinary medicine and an underdiagnosed zoonosis, mainly due to the lack of control and prevention initiatives, which consequently leads to a lack of public awareness. In the states of Pernambuco, Rio de Janeiro and in some cities in states of São Paulo, Minas Gerais Bahia, Rio Grande do Norte and Paraíba have compulsory notification of cases. Since December 1, 2020, the notification of sporotrichosis in dogs and cats has become mandatory in the city of São Paulo. The purpose of this review is to emphasize that sporotrichosis is an emerging zoonosis that is underdiagnosed in Brazil. Information and publicity campaigns are needed to reinforce the importance of treatment and the potential for a cure, as well as effective educational measures related to public health programs for the control of human and animal sporotrichosis. Responsible pet ownership campaigns, which emphasize the importance of neutering and restricting street access, are of paramount importance for the epidemiological control of the disease. Veterinarians have a fundamental role to play in guiding the guardian, emphasizing that the lack of treatment, in addition to causing great suffering to the affected animal, can contribute to the spread of the disease, including to humans.

Biological Control Ability and Antifungal Activities of Bacillus velezensis Bv S3 against Fusarium oxysporum That Causes Rice Seedling Blight

Fusarium oxysporum, a primary soil-borne fungus that affects rice seedlings globally, is responsible for rice seedling blight (RSB), which reduces seedling quality and survival rates. The synthetic fungicides used to treat this disease negatively affect human health and the environment. A biocontrol bacterial isolate, Bacillus velezensis Bv S3, isolated from the rice rhizosphere, showed a strong antagonistic effect on RSB-causing F. oxysporum. The ratio of the longest to the shortest radius of F. oxysporum following Bv S3 inoculation was 2.52 (cm/cm) in a plate standoff experiment. This was different from the other biocontrol strains. Bv S3 exhibits a wide spectrum of antifungal activity against various pathogenic fungi that cause RSB. When 10% Bv S3 liquid culture filtrate was applied, it dramatically reduced F. oxysporum spore germination and mycelial growth, with inhibition rates of 66.7%, and 45.7%, respectively, and caused hyphal malformations. Furthermore, the Bv S3 suspension (1 × 108 CFU/mL) reduced RSB by 65.5% and 76.5% in pot experiments, effectively promoted the growth of rice seedlings, and improved the activities of neutral phosphatase, urease, invertase, and catalase in rice rhizosphere soil. The active substances produced by Bv S3 were sensitive to temperature and ultraviolet irradiation, and the antifungal effect significantly increased after 90 min of exposure, with antifungal effect observed at pH 7. Bv. S3 effectively reduced the incidence of RSB and showed potential as a biocontrol agent.

Intravaginal Gel for Sustained Delivery of Occidiofungin and Long-Lasting Antifungal Effects.

Fungal infections are caused by opportunistic pathogens that can be life threatening or debilitating. Candida spp. are becoming increasingly resistant to current clinically approved antifungal therapeutics. Candida infections afflict not only immunosuppressed but also immunocompetent individuals. Recurrent vulvovaginal candidiasis (RVVC) is a disease that afflicts 5-9% of women. Occidiofungin is a novel cyclic peptide that has a broad spectrum of antifungal activity with a novel fungicidal mechanism of action. A gel formulation containing occidiofungin (OCF001) is being developed for use to treat vulvovaginal candidiasis. The formulated gel for intravaginal application used hydroxyethyl cellulose as the primary gelling agent and hydroxypropyl β-cyclodextrin as a solubilizing agent for occidiofungin. Franz cells and LC-MS/MS were used to determine the rate of drug substance diffusion in the gel formulation. The formulation was tested in an ex vivo mouse skin efficacy study, and the safety was tested following repeat intravaginal administration in rabbits. In this study, the gel formulation was shown to reduce the drug substance rate of diffusion across a skin memetic membrane. The study showed that the formulation extends exposure time to inhibitory concentrations of occidiofungin over a 24-h period and supports a single daily application for the treatment of RVVC.

High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms.

Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. Candida albicans remains the most frequent causative agent of candidiasis, but, in the last decade, C. auris has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. Here, we have screened the Repurposing Hub library from the Broad Institute, containing over 6000 compounds, in search for inhibitors of C. albicans and C. auris biofilm formation. The primary screen identified 57 initial hits against C. albicans and 33 against C. auris. Confirmatory concentration-dependent assays were used to validate the activity of the initial hits and, at the same time, establish their anti-biofilm potency. Based on these results, ebselen, temsirolimus, and compound BAY 11-7082 emerged as the leading repositionable compounds. Subsequent experiments established their spectrum of antifungal activity against yeasts and filamentous fungi. In addition, their in vivo activity was examined in the murine models of hematogenously disseminated C. albicans and C. auris infections. Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections.

Assessment of Antifungal Properties of the Exudate Gel from the Stem of Caralluma retrospiciens Against Clinical Isolate of Candida albicans

The desert plant C. retrospiciens (Ehrenb.) is an inhabitant of the southern region of Kingdom of Saudi Arabia (KSA). The stem of C. retrospiciens produces a gel which is often applied by local people to cure wounds. This study was aimed at determination of the antifungal effect of the exudate gel (EG) against Candida albicans (C. albicans). The antifungal activity of EG was measured using agar well diffusion method. Results showed excellent antifungal activity of the exudate gel. The spectrum of antifungal activity of EG against C. albicans was almost equivalent to that of standard amphotericin B, with statistical insignificance (p < 0.05).

Novel pyrazole-4-carboxamides and aromatic carboxamides derivatives containing a hydrazine moiety as potential SDHIs

To promote the discovery and development of novel SDHIs fungicides, a series of novel pyrazole-4-carboxamides 4a-t and aromatic carboxamides 8a-i with a hydrazine scaffold were designed, synthesized, and evaluated for their antifungal activities. The results showed that compound 4i exhibited outstanding antifungal activity against R. solani with EC50 value of 0.24 μg/mL, which was about three times more potent than that of Boscalid (EC50 = 0.74 μg/mL). Moreover, compound 4i also displayed promising antifungal activities against Sclerotinia sclerotiorum, B. cinerea, Alternaria alternate, and F. graminearum (IC50 = 1.21–4.50 μg/mL), indicating a broad spectrum of antifungal activities. Additionally, in vivo antifungal activities results showed that 4i could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (55.21%) and excellent curative efficacy (73.06%) at 100 μg/mL. The results of the SDH enzymatic inhibition assay showed that compound 4i generated significant SDH inhibition with IC50 value of 6.47 μM, which was superior to Boscalid (IC50 = 7.92 μM). Furthermore, SEM analysis showed that compound 4i could remarkably disrupt the typical structure and morphology of R. solani hyphae. The molecular docking study revealed that compound 4i could form H-bonds interactions and π-π interactions with TRP173 and TRY58 at the activity site of SDH, which was similar to that of Boscalid. The DFT calculation provided crucial information regarding electron transfer, which was essential in understanding the mechanism of molecules and target enzymes. These results indicated that compound 4i showed potential as a SDHIs fungicide and warranted further investigation.

Screening the medicine for malaria venture's Pandemic Response Box to identify novel inhibitors of Candida albicans and Candida auris biofilm formation.

Candida spp. are opportunistic yeasts capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. We screened the Pandemic Response Box containing 400 diverse drug-like molecules active against bacteria, viruses or fungi, for inhibitors of Candida albicans and Candida auris biofilm formation. Initial hits were identified based on the demonstration of >70% inhibitory activity. Dose-response assays were used to confirm the antifungal activity of initial hits and establish their potency. The spectrum of antifungal activity of the leading compounds was determined against a panel of medically important fungi, and the in vivo activity of the leading repositionable agent was evaluated in murine models of C. albicans and C. auris systemic candidiasis. The primary screening identified 20 hit compounds, and their antifungal activity and potency against C. albicans and C. auris were validated using dose-response measurements. From these experiments, the rapalog everolimus, emerged as the leading repositionable candidate. Everolimus displayed potent antifungal activity against different Candida spp., but more moderate levels of activity against filamentous fungi. Treatment with everolimus increased survival of mice infected with C. albicans, but not those with C. auris. The screening of the Pandemic Response Box resulted in the identification of several drugs with novel antifungal activity, with everolimus emerging as the main repositionable candidate. Further in vitro and in vivo studies are needed to confirm its potential therapeutic use.

Physicochemical and Anti-fungal Studies of the Pharmaceutical Co-crystal/Salt of Fluconazole.

Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt's thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π-π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains (Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.

New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis

This work describes the design, synthesis and antifungal activity of new imidazoles and 1,2,4-triazoles derived from eugenol and dihydroeugenol. These new compounds were fully characterized by spectroscopy/spectrometric analyses and the imidazoles 9, 10, 13 e 14 showed relevant antifungal activity against Candida sp. and Cryptococcus gattii in the range of 4.6–75.3 μM. Although no compound has shown a broad spectrum of antifungal activity against all evaluated strains, some azoles were more active than either reference drugs employed against specific strains. Eugenol-imidazole 13 was the most promising azole (MIC: 4.6 μM) against Candida albicans being 32 times more potent than miconazole (MIC: 150.2 μM) with no relevant cytotoxicity (selectivity index >28). Notably, dihydroeugenol-imidazole 14 was twice as potent (MIC: 36.4 μM) as miconazole (MIC: 74.9 μM) and more than 5 times more active than fluconazole (MIC: 209.0 μM) against alarming multi-resistant Candida auris. Furthermore, in vitro assays showed that most active compounds 10 and 13 altered the fungal ergosterol biosynthesis, reducing its content as fluconazole does, suggesting the enzyme lanosterol 14α-demethylase (CYP51) as a possible target for these new compounds. Docking studies with CYP51 revealed an interaction between the imidazole ring of the active substances with the heme group, as well as insertion of the chlorinated ring into a hydrophobic cavity at the binding site, consistent with the behavior observed with control drugs miconazole and fluconazole. The increase of azoles-resistant isolates of Candida species and the impact that C. auris has had on hospitals around the world reinforces the importance of discovery of azoles 9, 10, 13 e 14 as new bioactive compounds for further chemical optimization to afford new clinically antifungal agents.

Screening for Antifungal Indigenous Lactobacilli Strains Isolated from Local Fermented Milk for Developing Bioprotective Fermentates and Coatings Based on Acid Whey Protein Concentrate for Fresh Cheese Quality Maintenance.

The demand for healthy foods without artificial food additives is constantly increasing. Hence, natural food preservation methods using bioprotective cultures could be an alternative to chemical preservatives. Thus, the main purpose of this work was to screen the indigenous lactobacilli isolated from fermented cow milk for their safety and antifungal activity to select the safe strain with the strongest fungicidal properties for the development of bioprotective acid whey protein concentrate (AWPC) based fermentates and their coatings intended for fresh cheese quality maintenance. Therefore, 12 lactobacilli strains were isolated and identified from raw fermented cow milk as protective cultures. The safety of the stains was determined by applying antibiotic susceptibility, haemolytic and enzymatic evaluation. Only one strain, Lacticaseibacillus paracasei A11, met all safety requirements and demonstrated a broad spectrum of antifungal activity in vitro. The strain was cultivated in AWPC for 48 h and grew well (biomass yield 8 log10 cfu mL-1). L. paracasei A11 AWPC fermentate was used as a vehicle for protective culture in the development of pectin-AWPC-based edible coating. Both the fermentate and coating were tested for their antimicrobial properties on fresh acid-curd cheese. Coating with L. paracasei A11 strain reduced yeast and mould counts by 1.0-1.5 log10 cfu mL-1 (p ≤ 0.001) during cheese storage (14 days), simultaneously preserving its flavour and prolonging the shelf life for six days.

Anti-phytopathogenic activity and the mechanisms of phthalides from Angelica sinensis (Oliv.) Diels.

The resistance of traditional chemical fungicides to plant pathogenic fungi and the threats to the safety of humans and the environment highlight an urgent need to find safe and efficient alternatives to chemical fungicides. Owing to the wide spectrum of antifungal activities, low persistence and nontoxicity to mammals and aquatic life, essential oils have considerable potential as low-risk pesticides. In this study, the essential oil and the main components of Angelica sinensis (Oliv.) Diels (Danggui) were extracted, analyzed by GC-MS, and evaluated for their antifungal activities against six plant pathogenic fungi. 3-butylidenephthalide (3-BPH) showed the best antifungal activity against Fusarium graminearum with an EC50 value of 14.35 μg mL-1 . The antifungal mechanistic studies revealed that 3-BPH induced the generation of endogenous ROS to cause lipid peroxidation of the cell membrane and inhibited the biosynthesis of ergosterol, thereby causing the cell membranedamaged to exert its fungicidal activity. Significantly, 3-BPH could reduce deoxynivalenol production compared to the control. This study demonstrated the potent fungicidal activity of natural phthalide compound 3-BPH and highlighted its potential as an alternative agent to control F. graminearum. © 2023 Society of Chemical Industry.

Liposomal amphotericin B-the present.

Most invasive fungal infections are opportunistic in nature but the epidemiology is constantly changing, with new risk groups being identified. Neutropenia is a classical risk factor for fungal infections, while critically ill patients in the ICU are now increasingly at risk of yeast and mould infections. Factors to be considered when choosing antifungal treatment include the emergence of rarer fungal pathogens, the risk of resistance to azoles and echinocandins and the possibility of drug-drug interactions. Liposomal amphotericin B has retained its place in the therapeutic armamentarium based on its clinical profile: a broad spectrum of antifungal activity with a low risk of resistance, predictable pharmacokinetics with a rapid accumulation at the infection site (including biofilms), a low potential for drug-drug interactions and a low risk of acute and chronic treatment-limiting toxicities versus other formulations of amphotericin B. It is a suitable choice for the first-line empirical or pre-emptive treatment of suspected fungal infections in neutropenic haematology patients and is an excellent alternative for patients with documented fungal disease who can no longer tolerate or continue their first-line azole or echinocandin therapy, both in the haematology setting and in the ICU. Moreover, it is the first-line drug of choice for the treatment of invasive mucormycosis. Finally, liposomal amphotericin B is one of the few antifungal agents approved for use in children of all ages over 1 month and is included in paediatric-specific guidelines for the management of fungal disease.

INHIBITORY EFFECT OF ANTIFUNGAL ACTIVITY OF GROUND NUT OIL AGENT’S FUNGI

Ground nut (Arachis hypogaea) oil is essential component of our food and it can inhibit the spore germination of Aspergillus sp. The development of protective components with natural origin as alternatives to synthetic fungicides is currently in the spotlight. This oil is known for their broad spectrum of antifungal activity against plant pathogen and human both. The essential oils reduce hyphal growth and induce cell lysis and cytoplasmic evacuation in fungi.

Amphotericin B and 5-flucytosine as fungicides against Penicillium italicum for citrus fruit rot

The expansion of the global population and improved living standards has created an increasing demand for fresh fruit. The combination of agricultural and medical development for new fungicides is one of the most effective approaches for keeping fruit fresh. Both amphotericin B and 5-flucytosine are quite safe and have a wide spectrum of antifungal activity. For the purpose of investigating their potential applications for preserving fruit freshness, we evaluated their antifungal efficiencies against Penicillium italicum in vitro and in vivo. The results showed that amphotericin B and 5-flucytosine significantly inhibited spore germination and the mycelial growth of P. italicum. The 5-flucytosine showed much better bioactivity than the well-known agricultural fungicide prochloraz, both in vitro and in vivo. Furthermore, crystal violet staining, propidium iodide dyeing, ultrastructural observation and the ergosterol content indicated that amphotericin B and 5-flucytosine destroyed the cellular ultrastructure and membrane integrity. In addition, nucleic acids (OD260) and proteins (OD280) escaped from P. italicum cells in a dose-dependent manner. The results of this study indicated that amphotericin B and 5-flucytosine have good potential as antifungal preservatives for postharvest citrus fruit due to their excellent antifungal effects, and that the primary mode of action was the destruction of the membrane integrity and permeability of P. italicum.

New Developments in Pediatric Antifungal Pharmacology.

New Developments in Pediatric Antifungal Pharmacology.

Curvicollide D, a new modified γ-lactone from the culture broth of Albifimbria verrucaria and its antifungal activity against plant pathogenic fungi.

In our screening program for new antifungal active compounds, a new modified γ-lactone curvicollide D (1) together with five known trichothecenes (2-6) were isolated from the culture filtrate of fungus Albifimbria verrucaria based on the in vitro antifungal assay. The chemical structure of new compound 1 was elucidated by NMR and HR-MS spectroscopic analyses, and the relative configurations of 1 were deduced from NOE experiments and coupling constant analysis. Compound 1 exhibited moderate antifungal activities against plant pathogenic fungi Botrytis cinerea, Colletotrichum coccodes, and Magnaporthe oryzae with MIC value in a range of 100-200 µg ml-1. Moreover, trichothecene compounds (2-6) displayed a broad spectrum of antifungal activities with MIC values in a range of 6.3-100 µg ml-1.

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors.

Up to now, a total of 24 succinate dehydrogenase inhibitors (SDHIs) fungicides have been commercialized, and SDHIs fungicides were also one of the most active fungicides developed in recent years. Carboxamide derivatives represented an important class of SDHIs with broad spectrum of antifungal activities. In this review, the development of carboxamide derivatives as SDHIs with great significances were summarized. In addition, the structure-activity relationships (SARs) of antifungal activities of carboxamide derivatives as SDHIs was also summarized based on the analysis of the structures of the commercial SDHIs and lead compounds. Moreover, the cause of resistance of SDHIs and some solutions were also introduced. Finally, the development trend of SDHIs fungicides was prospected. We hope this review will give a guide for the development of novel SDHIs fungicides in the future.

Pharmaceutical co-crystals of posaconazole for improvement of physicochemical properties

Posaconazole exerts an extended spectrum of antifungal activity against various strains of clinically relevant moulds and yeasts. In recent years, antifungal triazole posaconazole has become increasingly important for the prophylaxis and treatment of systemic mycoses. After oral administration of posaconazole, absolute bioavailability has been estimated to range from 8% to 47%. Pharmaceutical co-crystallization is a promising approach for improving dissolution rate or manipulating other physical properties of API. The objective of this study is to improve the dissolution rate of posaconazole by co-crystallization. A 1:1 stoichiometric co-crystals of adipic acid were prepared by solvent assisted grinding method. The prepared co-crystals were subjected to solid-state characterization by FTIR, PXRD and DSC studies. The physicochemical properties of posaconazole and co-crystals were assessed in terms of melting point, flowability and dissolution rate. The results indicated improvement in flow property and dissolution rate. In vitro dissolution profile of co-crystals showed a significant increased dissolution of posaconazole from initial period in 0.1 N hydrochloric acid solution. The dissolution efficiency for posaconazole-adipic acid co-crystal was 61.65 % against posaconazole, 46.58 %. Thus, co-crystallization can be a promising approach to prepare posaconazole-adipic acid co-crystals with improved physicochemical properties.

The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts.

Phytopathogenic fungi infect crops, presenting a worldwide threat to agriculture. Polyene macrolides are one of the most effective antifungal agents applied in human therapy and crop protection. In this study, we found a cryptic polyene biosynthetic gene cluster in Actinokineospora spheciospongiae by genome mining. Then, this gene cluster was activated via varying fermentation conditions, leading to the discovery of new polyene actinospene (1), which was subsequently isolated and its structure determined through spectroscopic techniques including UV, HR-MS, and NMR. The absolute configuration was confirmed by comparing the calculated and experimental electronic circular dichroism (ECD) spectra. Unlike known polyene macrolides, actinospene (1) demonstrated more versatile post-assembling decorations including two epoxide groups and an unusual isobutenyl side chain. In bioassays, actinospene (1) showed a broad spectrum of antifungal activity against several plant fungal pathogens as well as pathogenic yeasts with minimum inhibitory concentrations ranging between 2 and 10 μg/mL.