A Decade of Antifungal Leads from Natural Products (original) (raw)
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Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source.
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A new spectrum of human fungal infections is increasing due to increased cancer, AIDS, and immunocompromised patients. The increased use of antifungal agents also resulted in the development of resistance to the present drugs. It makes necessary to discover new classes of antifungal compounds to cure fungal infections. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, saponins, alkaloids, flavonoids, and other compounds, reported to have in vitro antifungal properties. Since the plant kingdom provides a useful source of lead compounds of novel structure, a wide-scale investigation of species from the tropics has been considered. Therefore, the research on natural products and compounds derived from natural products has accelerated in recent years due to their importance in drug discovery. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans. These molecules may be used directly or considered as a precursor for developing better molecules. This review attempts to summarize the current status of important antifungal compounds from plants.
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The vast number and variety of chemotherapeutic agents isolated from microbial natural products and used to treat bacterial infections have greatly contributed to the improvement of human health during the past century. However, only a limited number of antifungal agents (polyenes and azoles, plus the recently introduced caspofungin acetate) are currently available for the treatment of life-threatening fungal infections. Furthermore, the prevalence of systemic fungal infections has increased significantly during the past decade. For this reason, the development of new antifungal agents, preferably with novel mechanisms of action, is an urgent medical need. A selection of antifungal agents in early stages of development, produced by microorganisms , is summarized in this review. The compounds are classified according to their mechanisms of action, covering inhibitors of the synthesis of cell wall components (glucan, chitin and mannoproteins), of sphingolipid synthesis (serine palmitoyltransferase, ceramide synthase, inositol phosphoceramide synthase and fatty acid elongation) and of protein synthesis (sordarins). In addition, some considerations related to the chemotaxonomy of the producing organisms and some issues relevant to antifungal drug discovery are also discussed.
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Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates.
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Due to the increase of the incidence of fungal infections in humans and the limitations of the available antimycotic drugs, among which the emergence of resistant strains, there is a need for the discovery of new antifungal agents. Plants, especially those used in Traditional Medicine, linked to an unmatched chemical diversity, either as pure compounds or as plant extracts, provide unlimited opportunities for the development of new antifungals. In recent years, compounds from different phytochemical groups have been described as having antifungal activity, including polyphenols, saponins, or peptides, among others, as well as essential oils and their constituents. After screening of ethnopharmacologically selected plants, mainly from Latin-America, followed by bio-guided isolation, our group has described the antifungal activity of different types of plant constituents, such as sesquiterpenes, triterpenes, flavonoids, lignans, fatty acids and essential oils.
9. Natural products: Anti-fungal agents derived from plants
As new spectrums of human fungal infections are increasing due to increased cancer and AIDS patients. The increased use of antifungal agents also resulted in the development of resistance to these drugs. It makes necessary to discover new classes of antifungal compounds to treat fungal infections. The research on natural products and natural products derived compounds has accelerated in recent years due to their importance in drug discovery. Plants are rich source of bioactive secondary metabolites of wide variety such as tannins, terpenoids, alkaloids, and flavonoids, reported to have in vitro antifungal properties. A series of molecules with antifungal activity against different strains of fungus have been found in plants, which are of great importance to humans and plants. These molecules may be used directly or considered as a model for developing better molecules. This review attempts to summarize the current status of reported antifungal compounds from plants.
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The need for new antifungal agents continues, fueled by opportunistic infections in immunecompromised patients and by the development of resistance to existing agents. Natural products offer a virtually unlimited source of unique molecules and not only serve as a reservoir for new potential drugs and drug prototypes, but also for probes of fungal biology. In this chapter, whole-cell screening methods targeted for natural products are illustrated, including general microplate-based screening, bioautography, and mode of action studies, including the use of genetically altered fungal strains now available commercially.