Enhanced activity of strobilurin and fludioxonil by using berberine and phenolic compounds to target fungal antioxidative stress response

Kim, J.H.; Campbell, Bruce; Mahoney, Noreen; Chan, Kathleen L.; Molyneux, Russell J.; May, Gregory S.

doi:10.1111/j.1472-765x.2007.02159.x

Cited by 40 publications

(28 citation statements)

References 32 publications

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“…Such a strategy is called chemosensitization. One concept underlying the selection of putative chemosensitizers consists of increasing fungitoxic activity by disrupting fungal oxidative stress-response systems that protect the fungus from reactive oxygen species (ROS; Kim et al, 2006a, 2007, 2011). This approach has been demonstrated in vitro successfully by assays that include fungicides/antibiotics with compounds that disrupt the oxygen stress-response system, enhancing sensitivity of mycotoxigenic fungi and human pathogenic fungi of medical importance to antifungal agents (Kim et al, 2006b, 2008; Faria et al, 2011; Kim and Campbell, 2011).…”

Section: Discussionmentioning

confidence: 99%

Chemosensitization of Plant Pathogenic Fungi to Agricultural Fungicides

Dzhavakhiya¹,

Щербакова²,

Semina³

et al. 2012

Front. Microbio.

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A common consequence of using agricultural fungicides is the development of resistance by fungal pathogens, which undermines reliability of fungicidal effectiveness. A potentially new strategy to aid in overcoming or minimizing this problem is enhancement of pathogen sensitivity to fungicides, or “chemosensitization.” Chemosensitization can be accomplished by combining a commercial fungicide with a certain non- or marginally fungicidal substance at levels where, alone, neither compound would be effective. Chemosensitization decreases the probability of the pathogen developing resistance, reduces the toxic impact on the environment by lowering effective dosage levels of toxic fungicides, and improves efficacy of antifungal agents. The present study shows that the antifungal activity of azole and strobilurin fungicides can be significantly enhanced through their co-application with certain natural or synthetic products against several economically important plant pathogenic fungi. Quadris (azoxystrobin) combined with thymol at a non-fungitoxic concentration produced much higher growth inhibition of Bipolaris sorokiniana, Phoma glomerata, Alternaria sp. and Stagonospora nodorum than the fungicide alone. The effect of Dividend (difenoconazole) applied with thymol significantly enhanced antifungal activity against B. sorokiniana and S. nodorum. Folicur (tebuconazole) combined with 4-hydroxybenzaldehyde (4-HBA), 2,3-dihydroxybenzaldehyde or thymol significantly inhibited growth of Alternaria alternata, at a much greater level than the fungicide alone. In addition, co-application of Folicur and 4-HBA resulted in a similar enhancement of antifungal activity against Fusarium culmorum. Lastly, we discovered that metabolites in the culture liquid of Fusarium sambucinum biocontrol isolate FS-94 also had chemosensitizing activity, increasing S. nodorum sensitivity to Folicur and Dividend.

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Section: Discussionmentioning

confidence: 99%

Chemosensitization of Plant Pathogenic Fungi to Agricultural Fungicides

Dzhavakhiya¹,

Щербакова²,

Semina³

et al. 2012

Front. Microbio.

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“…The initial discovery of natural products as chemosensitizing agents involved commercial agricultural fungicides (Kim et al. 2006, 2007, 2008b).…”

Section: Discussionmentioning

confidence: 99%

Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

Faria

Kim

Gonçalves

et al. 2011

Letters in Applied Microbiology

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Aims: Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. Methods and Results: Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3‐ and 2,5‐dihydroxybenzaldehydes (‐DBA) had synergistic interactions depending upon drug and yeast strain. 2,5‐DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. Conclusions: Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. Significance and Impact of the Study: This is a proof‐of‐concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.

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“…Additional natural compounds were also found to enhance activity of commercial fungicides. These included the alkaloid, berberine, and several phenolic compounds, enhancing antifungal activity of fludioxonil and strobilurin against A. flavus by further disrupting its oxidative stress response system (Kim et al, 2007a). Also tested were 2,3-dihydroxybenzaldehyde, salicylaldehyde and other benzo analogs.…”

Section: Chemosensitization Of Antifungal Agentsmentioning

confidence: 99%

“…The study showed that berberine disrupted Mn-SOD (mitochondrial superoxide dismutase) required for detoxification of ROS produced from the inhibition of mitochondrial respiration by strobilurin. Furthermore, this additional oxidative stress induced by berberine also resulted in overcoming resistance to fludioxonil (Kim et al, 2007a). …”

Section: Chemosensitization Of Antifungal Agentsmentioning

confidence: 99%

Chemosensitization as a Means to Augment Commercial Antifungal Agents

2012

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Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance.

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Enhanced activity of strobilurin and fludioxonil by using berberine and phenolic compounds to target fungal antioxidative stress response

Cited by 40 publications

References 32 publications

Chemosensitization of Plant Pathogenic Fungi to Agricultural Fungicides

Chemosensitization of Plant Pathogenic Fungi to Agricultural Fungicides

Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

Chemosensitization as a Means to Augment Commercial Antifungal Agents

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