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      The Antifungal Activity of Naphthoquinones: An Integrative Review

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          Abstract

          ABSTRACT Naphthoquinones are the most commonly occurring type of quinones in nature. They are a diverse family of secondary metabolites that occur naturally in plants, lichens and various microorganisms. This subgroup is constantly being expanded through the discovery of new natural products and by the synthesis of new compounds via innovative techniques. Interest in quinones and the search for new biological activities within the members of this class have intensified in recent years, as evidenced by the evaluation of the potential antimicrobial activities of quinones. Among fungi of medical interest, yeasts of the genus Candida are of extreme importance due to their high frequency of colonization and infection in humans. The objective of this review is to describe the development of naphthoquinones as antifungals for the treatment of Candida species and to note the most promising compounds. By using certain criteria for selection of publications, 68 reports involving both synthetic and natural naphthoquinones are discussed. The activities of a large number of substances were evaluated against Candida albicans as well as against 7 other species of the genus Candida. The results discussed in this review allowed the identification of 30 naphthoquinones with higher antifungal activities than those of the currently used drugs.

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          Natural products as leads to anticancer drugs.

          Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.
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            Natural products to drugs: natural product-derived compounds in clinical trials.

            Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.
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              Emerging Threats in Antifungal-Resistant Fungal Pathogens

              The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is tempting to combine several drugs to achieve better therapeutic efficacy. In the recent years, several novel resistance patterns have been observed, including antifungal resistance originating from environmental sources in Aspergillus fumigatus and the emergence of simultaneous resistance to different antifungal classes (multidrug resistance) in different Candida species. This review will summarize these current trends.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                aabc
                Anais da Academia Brasileira de Ciências
                An. Acad. Bras. Ciênc.
                Academia Brasileira de Ciências (Rio de Janeiro, RJ, Brazil )
                0001-3765
                1678-2690
                2018
                : 90
                : 1 suppl 2
                : 1187-1214
                Affiliations
                [2] Niterói Rio de Janeiro orgnameUniversidade Federal Fluminense orgdiv1Faculdade de Farmácia orgdiv2PPGCAPS Brazil
                [4] Rio de Janeiro Rio de Janeiro orgnameUniversidade Federal do Rio de Janeiro orgdiv1Instituto de Biofísica Carlos Chagas Filho orgdiv2Centro de Ciências da Saúde Brazil
                [1] Niterói Rio de Janeiro orgnameUniversidade Federal Fluminense orgdiv1Faculdade de Farmácia orgdiv2Departamento de Tecnologia Farmacêutica Brazil
                [3] Niterói Rio de Janeiro orgnameUniversidade Federal Fluminense orgdiv1Instituto de Química orgdiv2Departamento de Química Orgânica Brazil
                Article
                S0001-37652018000301187
                10.1590/0001-3765201820170815
                29873671
                6c8c4754-137e-4ac3-9fbe-dab562c73dff

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 11 October 2017
                : 08 December 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 170, Pages: 28
                Product

                SciELO Brazil


                Candida spp,disc diffusion method,Quinones,xanthenes,lapachol,lawsone

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