Conventional and natural compounds for the treatment of dermatophytosis

2019 ◽  
Vol 58 (6) ◽  
pp. 707-720
Author(s):  
Ana I Lopes ◽  
Freni K Tavaria ◽  
Manuela E Pintado
Keyword(s):  
Side Effects ◽  
Stratum Corneum ◽  
State Of The Art ◽  
Pathogenic Fungi ◽  
Resistance Mechanisms ◽  
Mechanisms Of Action ◽  
Antifungal Drugs ◽  
Skin Infections ◽  
Superficial Skin ◽  
High Treatment

Abstract Dermatophytes are a group of pathogenic fungi that exclusively infect the stratum corneum of the skin, nails, and hair, causing dermatophytosis. Superficial skin infections caused by dermatophytes have increased in the last decades. There are conventional antifungals that treat these infections, such as terbinafine, fluconazole, and others. However, the limitations of these treatments (resistance, side effects and toxicity) along with the increasing over-prescription, the misuse of these antifungals and the high treatment costs led to the search for new, alternative, natural-based antifungal drugs. These have multiple mechanisms of action, which works to their advantage, making it difficult for a fungus to create resistance mechanisms against all of them at the same time. The main objective of this work is to provide a state-of-the-art review on dermatophytes, dermatophytosis, and the existing treatments, both conventional and natural, such as chitosan and essential oils.

Setting New Routes for Antifungal Drug Discovery Against Pathogenic Fungi

2020 ◽  
Vol 26 (14) ◽  
pp. 1509-1520 ◽  
Author(s):  
Kleber S. Freitas e Silva ◽  
Lívia C. Silva ◽  
Relber A. Gonçales ◽  
Bruno J. Neves ◽  
Célia M.A. Soares ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Side Effects ◽  
Fungal Pathogens ◽  
Glyoxylate Cycle ◽  
Extended Period ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
The Glyoxylate Cycle

: Fungal diseases are life-threatening to human health and responsible for millions of deaths around the world. Fungal pathogens lead to a high number of morbidity and mortality. Current antifungal treatment comprises drugs, such as azoles, echinocandins, and polyenes and the cure is not guaranteed. In addition, such drugs are related to severe side effects and the treatment lasts for an extended period. Thus, setting new routes for the discovery of effective and safe antifungal drugs should be a priority within the health care system. The discovery of alternative and efficient antifungal drugs showing fewer side effects is time-consuming and remains a challenge. Natural products can be a source of antifungals and used in combinatorial therapy. The most important natural products are antifungal peptides, antifungal lectins, antifungal plants, and fungi secondary metabolites. Several proteins, enzymes, and metabolic pathways could be targets for the discovery of efficient inhibitor compounds and recently, heat shock proteins, calcineurin, salinomycin, the trehalose biosynthetic pathway, and the glyoxylate cycle have been investigated in several fungal species. HSP protein inhibitors and echinocandins have been shown to have a fungicidal effect against azole-resistant fungi strains. Transcriptomic and proteomic approaches have advanced antifungal drug discovery and pointed to new important specific-pathogen targets. Certain enzymes, such as those from the glyoxylate cycle, have been a target of antifungal compounds in several fungi species. Natural and synthetic compounds inhibited the activity of such enzymes and reduced the ability of fungal cells to transit from mycelium to yeast, proving to be promisor antifungal agents. Finally, computational biology has developed effective approaches, setting new routes for early antifungal drug discovery since normal approaches take several years from discovery to clinical use. Thus, the development of new antifungal strategies might reduce the therapeutic time and increase the quality of life of patients.

scholarly journals Antifungal Drugs

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 106 ◽  
Author(s):  
Jiří Houšť ◽  
Jaroslav Spížek ◽  
Vladimír Havlíček
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Drug Target ◽  
Deoxyribonucleic Acid ◽  
Enzyme Inhibitors ◽  
Efflux Pump ◽  
Mechanisms Of Action ◽  
Antifungal Drugs ◽  
Acid Biosynthesis ◽  
Glucan Synthase

We reviewed the licensed antifungal drugs and summarized their mechanisms of action, pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics inhibit 1,3-β-d-glucan synthase, lanosterol 14-α-demethylase, protein, and deoxyribonucleic acid biosynthesis, or sequestrate ergosterol. Their most severe side effects are hepatotoxicity, nephrotoxicity, and myelotoxicity. Whereas triazoles exhibit the most significant drug–drug interactions, echinocandins exhibit almost none. The antifungal resistance may be developed across most pathogens and includes drug target overexpression, efflux pump activation, and amino acid substitution. The experimental antifungal drugs in clinical trials are also reviewed. Siderophores in the Trojan horse approach or the application of siderophore biosynthesis enzyme inhibitors represent the most promising emerging antifungal therapies.

scholarly journals Pharmacological Overview of Galactogogues

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Felipe Penagos Tabares ◽  
Juliana V. Bedoya Jaramillo ◽  
Zulma Tatiana Ruiz-Cortés
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Milk Production ◽  
State Of The Art ◽  
Dairy Industry ◽  
Mechanisms Of Action ◽  
Human Medicine ◽  
Herbal Preparations ◽  
Increase Milk Production ◽  
Clinical Conditions

Galactogogues are substances used to induce, maintain, and increase milk production, both in human clinical conditions (like noninfectious agalactias and hypogalactias) and in massification of production in the animal dairy industry. This paper aims to report the state of the art on the possible mechanisms of action, effectiveness, and side effects of galactogogues, including potential uses in veterinary and human medicine. The knowledge gaps in veterinary clinical practice use of galactogogues, especially in the standardization of the lactogenic dose in some pure drugs and herbal preparations, are reviewed.

scholarly journals Carrier-Mediated Drug Uptake in Fungal Pathogens

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1324
Author(s):  
Mónica Galocha ◽  
Inês Vieira Costa ◽  
Miguel Cacho Teixeira
Keyword(s):  
Drug Resistance ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Pathogenic Fungi ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Major Facilitator Superfamily ◽  
Drug Uptake ◽  
Human Pathogens

Candida, Aspergillus, and Cryptococcus species are the most frequent cause of severe human fungal infections. Clinically relevant antifungal drugs are scarce, and their effectiveness are hampered by the ability of fungal cells to develop drug resistance mechanisms. Drug effectiveness and drug resistance in human pathogens is very often affected by their “transportome”. Many studies have covered a panoply of drug resistance mechanisms that depend on drug efflux pumps belonging to the ATP-Binding Cassette and Major Facilitator Superfamily. However, the study of drug uptake mechanisms has been, to some extent, overlooked in pathogenic fungi. This review focuses on discussing current knowledge on drug uptake systems in fungal pathogens, highlighting the need for further studies on this topic of great importance. The following subjects are covered: (i) drugs imported by known transporter(s) in pathogenic fungi; and (ii) drugs imported by known transporter(s) in the model yeast Saccharomyces cerevisiae or in human parasites, aimed at the identification of their homologs in pathogenic fungi. Besides its contribution to increase the understanding of drug-pathogen interactions, the practical implications of identifying drug importers in human pathogens are discussed, particularly focusing on drug development strategies.

Dexamethasone-Chemical Structure and Mechanisms of Action in Prophylaxis of Postoperative Side Effects

2019 ◽  
Vol 70 (3) ◽  
pp. 843-847 ◽  
Author(s):  
Oana Roxana Ciobotaru ◽  
Mary-Nicoleta Lupu ◽  
Laura Rebegea ◽  
Octavian Catalin Ciobotaru ◽  
Oana Monica Duca ◽  
...  
Keyword(s):  
Wound Healing ◽  
Side Effects ◽  
Length Of Stay ◽  
Hospital Admission ◽  
Postoperative Period ◽  
Analgesic Effect ◽  
Chemical Structure ◽  
Mechanisms Of Action ◽  
Good Recovery ◽  
Synthetic Glucocorticoid

Dexamethasone is a synthetic glucocorticoid used for its anti-inflammatory and analgesic effect. In addition to these therapeutic indications, it is also recommended for nausea and vomiting treatment which may occur during the postoperative period, with impact on postoperative evolution, regarding the evolution of wound healing and length of stay (LOS), with a reflection on the costs of hospital admission. Therefore, their prevention is very important for both patients� comfort and a good recovery.

Fungal Phytotoxins in Sustainable Weed Management

2018 ◽  
Vol 25 (2) ◽  
pp. 268-286 ◽  
Author(s):  
Maurizio Vurro ◽  
Angela Boari ◽  
Francesca Casella ◽  
Maria Chiara Zonno
Keyword(s):  
Weed Management ◽  
Pathogenic Fungi ◽  
Mechanisms Of Action ◽  
Limiting Factors ◽  
Integrated Weed Management ◽  
Plant Pathogenic Fungi ◽  
Design Strategies ◽  
Disease Etiology ◽  
Chemical Structures ◽  
Toxic Metabolites

Fungal phytotoxins are natural secondary metabolites produced by plant pathogenic fungi during host–pathogen interactions. They have received considerable particular attention for elucidating disease etiology, and consequently to design strategies for disease control. Due to wide differences in their chemical structures, these toxic metabolites have different ecological and environmental roles and mechanisms of action. This review aims at summarizing the studies on the possible use of these metabolites as tools in biological and integrated weed management, e.g. as: novel and environmentally friendly herbicides; lead for novel compounds; sources of novel mechanisms of action. Moreover, the limiting factors for utilizing those metabolites in practice will also be briefly discussed.

Progress on the Mechanism for Aspirin’s Anti-tumor Effects

2020 ◽  
Vol 22 (1) ◽  
pp. 105-111
Author(s):  
Lin Zheng ◽  
Weibiao Lv ◽  
Yuanqing Zhou ◽  
Xu Lin ◽  
Jie Yao
Keyword(s):  
Platelet Aggregation ◽  
Energy Metabolism ◽  
Side Effects ◽  
Energy Production ◽  
Immune Escape ◽  
Inflammatory Responses ◽  
Mechanisms Of Action ◽  
Proliferation And Metastasis ◽  
Review Current ◽  
Granule Release

: Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition to these applications, it is increasingly becoming clear that the drug also has great potential in the field of cancer. Here, we briefly review current insights of aspirin’s anti-tumor effects. These are multiple and vary from inhibiting the major cellular mTOR pathways, acting as a calorie-restricted mimetic by inhibition of energy production, suppressing platelet aggregation and granule release, inhibiting immune escape of tumor cells, to decreasing inflammatory responses. We consider these five mechanisms of action the most significant of aspirin’s anti-tumor effects, whereby the anti-tumor effect may ultimately stem from its inhibition of energy metabolism, platelet function, and inflammatory response. As such, aspirin can play an important role to reduce the occurrence, proliferation, and metastasis of various types of tumors. However, most of the collected data are still based on epidemiological investi-gations. More direct and effective evidence is needed, and the side effects of aspirin intake need to be solved before this drug can be widely applied in cancer treatment.

Biological Production of (S)-acetoin: A State-of-the-Art Review

2019 ◽  
Vol 19 (25) ◽  
pp. 2348-2356 ◽  
Author(s):  
Neng-Zhong Xie ◽  
Jian-Xiu Li ◽  
Ri-Bo Huang
Keyword(s):  
Side Effects ◽  
Chemical Synthesis ◽  
State Of The Art ◽  
Optically Active ◽  
Considerable Progress ◽  
Future Prospects ◽  
Chiral Compound ◽  
Biological Production ◽  
Acetoin Production ◽  
Made In

Acetoin is an important four-carbon compound that has many applications in foods, chemical synthesis, cosmetics, cigarettes, soaps, and detergents. Its stereoisomer (S)-acetoin, a high-value chiral compound, can also be used to synthesize optically active drugs, which could enhance targeting properties and reduce side effects. Recently, considerable progress has been made in the development of biotechnological routes for (S)-acetoin production. In this review, various strategies for biological (S)- acetoin production are summarized, and their constraints and possible solutions are described. Furthermore, future prospects of biological production of (S)-acetoin are discussed.

The Regulatory Function of the Molecular Chaperone Hsp90 in the Cell Wall Integrity of Pathogenic Fungi

2018 ◽  
Vol 16 (1) ◽  
pp. 44-53
Author(s):  
Marina Campos Rocha ◽  
Camilla Alves Santos ◽  
Iran Malavazi
Keyword(s):  
Cell Wall ◽  
Antifungal Therapy ◽  
Molecular Chaperone ◽  
Regulatory Protein ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Cell Wall Integrity ◽  
Regulatory Function ◽  
Loss Of Function ◽  
Hsp90 Inhibition

Different signaling cascades including the Cell Wall Integrity (CWI), the High Osmolarity Glycerol (HOG) and the Ca2+/calcineurin pathways control the cell wall biosynthesis and remodeling in fungi. Pathogenic fungi, such as Aspergillus fumigatus and Candida albicans, greatly rely on these signaling circuits to cope with different sources of stress, including the cell wall stress evoked by antifungal drugs and the host’s response during infection. Hsp90 has been proposed as an important regulatory protein and an attractive target for antifungal therapy since it stabilizes major effector proteins that act in the CWI, HOG and Ca2+/calcineurin pathways. Data from the human pathogen C. albicans have provided solid evidence that loss-of-function of Hsp90 impairs the evolution of resistance to azoles and echinocandin drugs. In A. fumigatus, Hsp90 is also required for cell wall integrity maintenance, reinforcing a coordinated function of the CWI pathway and this essential molecular chaperone. In this review, we focus on the current information about how Hsp90 impacts the aforementioned signaling pathways and consequently the homeostasis and maintenance of the cell wall, highlighting this cellular event as a key mechanism underlying antifungal therapy based on Hsp90 inhibition.

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

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