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1.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201401

RESUMO

The limited number of medicinal products available to treat of fungal infections makes control of fungal pathogens problematic, especially since the number of fungal resistance incidents increases. Given the high costs and slow development of new antifungal treatment options, repurposing of already known compounds is one of the proposed strategies. The objective of this study was to perform in vitro experimental tests of already identified lead compounds in our previous in silico drug repurposing study, which had been conducted on the known Drugbank database using a seven-step procedure which includes machine learning and molecular docking. This study identifies siramesine as a novel antifungal agent. This novel indication was confirmed through in vitro testing using several yeast species and one mold. The results showed susceptibility of Candida species to siramesine with MIC at concentration 12.5 µg/mL, whereas other candidates had no antifungal activity. Siramesine was also effective against in vitro biofilm formation and already formed biofilm was reduced following 24 h treatment with a MBEC range of 50-62.5 µg/mL. Siramesine is involved in modulation of ergosterol biosynthesis in vitro, which indicates it is a potential target for its antifungal activity. This implicates the possibility of siramesine repurposing, especially since there are already published data about nontoxicity. Following our in vitro results, we provide additional in depth in silico analysis of siramesine and compounds structurally similar to siramesine, providing an extended lead set for further preclinical and clinical investigation, which is needed to clearly define molecular targets and to elucidate its in vivo effectiveness as well.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Indóis/química , Indóis/farmacologia , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Simulação por Computador , Reposicionamento de Medicamentos/métodos , Ergosterol/metabolismo , Aprendizado de Máquina , Simulação de Acoplamento Molecular/métodos
2.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200814

RESUMO

Multi-drug resistant pathogens are a rising danger for the future of mankind. Iodine (I2) is a centuries-old microbicide, but leads to skin discoloration, irritation, and uncontrolled iodine release. Plants rich in phytochemicals have a long history in basic health care. Aloe Vera Barbadensis Miller (AV) and Salvia officinalis L. (Sage) are effectively utilized against different ailments. Previously, we investigated the antimicrobial activities of smart triiodides and iodinated AV hybrids. In this work, we combined iodine with Sage extracts and pure AV gel with polyvinylpyrrolidone (PVP) as an encapsulating and stabilizing agent. Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-Vis), Surface-Enhanced Raman Spectroscopy (SERS), microstructural analysis by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-Ray-Diffraction (XRD) analysis verified the composition of AV-PVP-Sage-I2. Antimicrobial properties were investigated by disc diffusion method against 10 reference microbial strains in comparison to gentamicin and nystatin. We impregnated surgical sutures with our biohybrid and tested their inhibitory effects. AV-PVP-Sage-I2 showed excellent to intermediate antimicrobial activity in discs and sutures. The iodine within the polymeric biomaterial AV-PVP-Sage-I2 and the synergistic action of the two plant extracts enhanced the microbial inhibition. Our compound has potential for use as an antifungal agent, disinfectant and coating material on sutures to prevent surgical site infections.


Assuntos
Antibacterianos/química , Antibacterianos/síntese química , Aloe/química , Antifúngicos/química , Gentamicinas/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura/métodos , Nistatina/química , Extratos Vegetais/química , Povidona/química , Salvia/química , Salvia officinalis/química , Espectrometria por Raios X/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
3.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202905

RESUMO

Cereals are subject to contamination by pathogenic fungi, which damage grains and threaten public health with their mycotoxins. Fusarium graminearum and its mycotoxins, trichothecenes B (TCTBs), are especially targeted in this study. Recently, the increased public and political awareness concerning environmental issues tends to limit the use of traditional fungicides against these pathogens in favor of eco-friendlier alternatives. This study focuses on the development of biofungicides based on the encapsulation of a curcumin derivative, tetrahydrocurcumin (THC), in polysaccharide matrices. Starch octenylsuccinate (OSA-starch) and chitosan have been chosen since they are generally recognized as safe. THC has been successfully trapped into particles obtained through a spray-drying or freeze-drying processes. The particles present different properties, as revealed by visual observations and scanning electron microscopy. They are also different in terms of the amount and the release of encapsulated THC. Although freeze-dried OSA-starch has better trapped THC, it seems less able to protect the phenolic compound than spray-dried particles. Chitosan particles, both spray-dried and lyophilized, have shown promising antifungal properties. The IC50 of THC-loaded spray-dried chitosan particles is as low as 0.6 ± 0.3 g/L. These particles have also significantly decreased the accumulation of TCTBs by 39%.


Assuntos
Antifúngicos , Agentes de Controle Biológico , Quitosana , Fusarium/crescimento & desenvolvimento , Amido/análogos & derivados , Antifúngicos/química , Antifúngicos/farmacologia , Agentes de Controle Biológico/química , Agentes de Controle Biológico/farmacologia , Quitosana/química , Quitosana/farmacologia , Curcumina/análogos & derivados , Curcumina/química , Curcumina/farmacologia , Amido/química , Amido/farmacologia
4.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071169

RESUMO

Polygodial is a "hot" peppery-tasting sesquiterpenoid that was first described for its anti-feedant activity against African armyworms. Using the haploid deletion mutant library of Saccharomyces cerevisiae, a genome-wide mutant screen was performed to shed more light on polygodial's antifungal mechanism of action. We identified 66 deletion strains that were hypersensitive and 47 that were highly resistant to polygodial treatment. Among the hypersensitive strains, an enrichment was found for genes required for vacuolar acidification, amino acid biosynthesis, nucleosome mobilization, the transcription mediator complex, autophagy and vesicular trafficking, while the resistant strains were enriched for genes encoding cytoskeleton-binding proteins, ribosomal proteins, mitochondrial matrix proteins, components of the heme activator protein (HAP) complex, and known regulators of the target of rapamycin complex 1 (TORC1) signaling. WE confirm that polygodial triggers a dose-dependent vacuolar alkalinization and that it increases Ca2+ influx and inhibits glucose-induced Ca2+ signaling. Moreover, we provide evidence suggesting that TORC1 signaling and its protective agent ubiquitin play a central role in polygodial resistance, suggesting that they can be targeted by polygodial either directly or via altered Ca2+ homeostasis.


Assuntos
Antifúngicos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Antifúngicos/química , Cálcio , Farmacorresistência Fúngica/genética , Homeostase/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Testes de Sensibilidade Microbiana , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Nucleossomos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Transdução de Sinais , ATPases Vacuolares Próton-Translocadoras
5.
Molecules ; 26(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069197

RESUMO

Ageratum conyzoides L. (Family-Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant's dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.


Assuntos
Ageratum/química , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Ageratum/classificação , Antifúngicos/efeitos adversos , Antifúngicos/química , Testes de Sensibilidade Microbiana , Metabolismo Secundário/efeitos dos fármacos
6.
AAPS PharmSciTech ; 22(5): 194, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184161

RESUMO

The study aimed to identify a suitable cosolvent + water mixture for subcutaneous (sub-Q) delivery of ketoconazole (KETO). The solubility was assessed for several dimethyl acetamide (DMA) + water mixtures at T = 293.2 to 318.2 K and pressure P = 0.1 MPa. The experimental solubility (xe) was validated using the Van 't Hoff and Yalkowsky models and functional thermodynamic parameters (enthalpy ΔsolH°, entropy ΔsolS°, and Gibbs free energy ΔsolG°). The in vitro drug release study was performed at physiological pH, and the data served as the input to GastroPlus, which predicted the in vivo performance of KETO dissolved in a DMA + water cosolvent mixture for sub-Q delivery in human. The maximum solubility (mole fraction) of KETO (9.81 × 10-1) was obtained for neat DMA at 318.2 K whereas the lowest value (1.7 × 10-5) was for pure water at 293.2 K. An apparent thermodynamic analysis based on xe gave positive values for the functional parameters. KETO dissolution requires energy, as evidenced by the high positive values of ΔsolH° and ΔsolG°. Interestingly, ΔsolG° progressively decreased with increasing concentration of DMA in the DMA + water mixture, suggesting that the DMA-based molecular interaction improved the solubilization. Positive values of ΔsolG° and ΔsolS° for each DMA + water cosolvent mixture corroborated the endothermic and entropy-driven dissolution. GastroPlus predicted better absorption of KETO through sub-Q delivery than oral delivery. Hence, the DMA + water mixture may be a promising system for sub-Q delivery of KETO to control topical and systemic fungal infections.


Assuntos
Antifúngicos/farmacocinética , Simulação por Computador , Cetoconazol/farmacocinética , Modelos Biológicos , Antifúngicos/química , Previsões , Humanos , Cetoconazol/química , Reprodutibilidade dos Testes , Solubilidade , Solventes/química , Solventes/farmacocinética , Água/química
7.
Int J Nanomedicine ; 16: 3091-3103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953557

RESUMO

Objective: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning. Methods: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro. Results: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 µg/mL and 20 µg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 µg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking. Significance: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Cetrimônio/química , Nanopartículas/química , Polimetil Metacrilato/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Técnicas de Química Sintética , Humanos , Nanotecnologia
8.
J Med Chem ; 64(10): 6706-6719, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34006103

RESUMO

Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors.


Assuntos
Antifúngicos/química , Ácido Aspártico Proteases/antagonistas & inibidores , Cryptococcus neoformans/enzimologia , Proteínas Fúngicas/antagonistas & inibidores , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Ácido Aspártico Proteases/genética , Ácido Aspártico Proteases/metabolismo , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fungos/efeitos dos fármacos , HIV/enzimologia , Protease de HIV/química , Protease de HIV/metabolismo , Simulação de Dinâmica Molecular , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Relação Estrutura-Atividade , Especificidade por Substrato
9.
Phytomedicine ; 88: 153556, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33958276

RESUMO

BACKGROUND: During the last three decades systemic fungal infections associated to immunosuppressive therapies have become a serious healthcare problem. Clinical development of new antifungals is an urgent requirement. Since fungal but not mammalian cells are encased in a carbohydrate-containing cell wall, which is required for the growth and viability of fungi, the inhibition of cell wall synthesizing machinery, such as ß(1,3)-D-glucan synthases (GS) and chitin synthases (CS) that catalyze the synthesis of ß(1-3)-D-glucan and chitin, respectively, represent an ideal mode of action of antifungal agents. Although the echinocandins anidulafungin, caspofungin and micafungin are clinically well-established GS inhibitors for the treatment of invasive fungal infections, much effort must still be made to identify inhibitors of other enzymes and processes involved in the synthesis of the fungal cell wall. PURPOSE: Since natural products (NPs) have been the source of several antifungals in clinical use and also have provided important scaffolds for the development of semisynthetic analogues, this review was devoted to investigate the advances made to date in the discovery of NPs from plants that showed capacity of inhibiting cell wall synthesis targets. The chemical characterization, specific target, discovery process, along with the stage of development are provided here. METHODS: An extensive systematic search for NPs against the cell wall was performed considering all the articles published until the end of 2020 through the following scientific databases: NCBI PubMed, Scopus and Google Scholar and using the combination of the terms "natural antifungals" and "plant extracts" with "fungal cell wall". RESULTS: The first part of this review introduces the state of the art of the structure and biosynthesis of the fungal cell wall and considers exclusively those naturally produced GS antifungals that have given rise to both existing semisynthetic approved drugs and those derivatives currently in clinical trials. According to their chemical structure, natural GS inhibitors can be classified as 1) cyclic lipopeptides, 2) glycolipids and 3) acidic terpenoids. We also included nikkomycins and polyoxins, NPs that inhibit the CS, which have traditionally been considered good candidates for antifungal drug development but have finally been discarded after enduring unsuccessful clinical trials. Finally, the review focuses in the most recent findings about the growing field of plant-derived molecules and extracts that exhibit activity against the fungal cell wall. Thus, this search yielded sixteen articles, nine of which deal with pure compounds and seven with plant extracts or fractions with proven activity against the fungal cell wall. Regarding the mechanism of action, seven (44%) produced GS inhibition while five (31%) inhibited CS. Some of them (56%) interfered with other components of the cell wall. Most of the analyzed articles refer to tests carried out in vitro and therefore are in early stages of development. CONCLUSION: This report delivers an overview about both existing natural antifungals targeting GS and CS activities and their mechanisms of action. It also presents recent discoveries on natural products that may be used as starting points for the development of potential selective and non-toxic antifungal drugs.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Produtos Biológicos/farmacologia , Parede Celular/efeitos dos fármacos , Fungos/citologia , Caspofungina/farmacologia , Parede Celular/química , Parede Celular/metabolismo , Quitina/biossíntese , Equinocandinas/farmacocinética , Fungos/efeitos dos fármacos , Glucanos/biossíntese , Glucosiltransferases/metabolismo , Humanos , Micoses/tratamento farmacológico
10.
AAPS PharmSciTech ; 22(4): 155, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33987739

RESUMO

The objectives of current investigation are (1) to find out wavelength of maximum absorbance (λmax) for combined cyclosporin A and etodolac solution followed by selection of mobile phase suitable for the RP-HPLC method, (2) to define analytical target profile and critical analytical attributes (CAAs) for the analytical quality by design, (3) to screen critical method parameters with the help of full factorial design followed by optimization with face-centered central composite design (CCD) approach-driven artificial neural network (ANN)-linked with the Levenberg-Marquardt (LM) algorithm for finding the RP-HPLC conditions, (4) to perform validation of analytical procedures (trueness, linearity, precision, robustness, specificity and sensitivity) using combined drug solution, and (5) to determine drug entrapment efficiency value in dual drug-loaded nanocapsules/emulsions, percentage recovery value in human plasma spiked with two drugs and solution state stability analysis at different stress conditions for substantiating the double-stage systematically optimized RP-HPLC method conditions. Through isobestic point and scouting step, 205 nm and ACN:H2O mixture (74:26) were selected respectively as the λmax and mobile phase. The ANN topology (3:10:4) indicating the input, hidden and output layers were generated by taking the 20 trials produced from the face-centered CCD model. The ANN-linked LM model produced minimal differences between predicted and observed values of output parameters (or CAAs), low mean squared error and higher correlation coefficient values in comparison to the respective values produced by face-centered CCD model. The optimized RP-HPLC method could be applied to analyze two drugs concurrently in different formulations, human plasma and solution state stability checking.


Assuntos
Ciclosporina/análise , Etodolac/análise , Aprendizado de Máquina , Nanocápsulas/análise , Redes Neurais de Computação , Algoritmos , Antifúngicos/análise , Antifúngicos/sangue , Antifúngicos/química , Inteligência Artificial/tendências , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Ciclosporina/sangue , Ciclosporina/química , Emulsões , Etodolac/sangue , Etodolac/química , Humanos , Aprendizado de Máquina/tendências , Nanocápsulas/química , Projetos de Pesquisa
11.
Int J Mol Sci ; 22(9)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1231493

RESUMO

Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported.


Assuntos
Antifúngicos/farmacologia , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Antifúngicos/química , Antifúngicos/uso terapêutico , Azóis/farmacologia , Candida/efeitos dos fármacos , Candidíase/microbiologia , Quimioterapia Combinada , Equinocandinas/farmacologia , Humanos , Micologia/métodos , Polienos/farmacologia , Falha de Tratamento
12.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1154456

RESUMO

Bats are unique in their potential to serve as reservoir hosts for intracellular pathogens. Recently, the impact of COVID-19 has relegated bats from biomedical darkness to the frontline of public health as bats are the natural reservoir of many viruses, including SARS-Cov-2. Many bat genomes have been sequenced recently, and sequences coding for antimicrobial peptides are available in the public databases. Here we provide a structural analysis of genome-predicted bat cathelicidins as components of their innate immunity. A total of 32 unique protein sequences were retrieved from the NCBI database. Interestingly, some bat species contained more than one cathelicidin. We examined the conserved cysteines within the cathelin-like domain and the peptide portion of each sequence and revealed phylogenetic relationships and structural dissimilarities. The antibacterial, antifungal, and antiviral activity of peptides was examined using bioinformatic tools. The peptides were modeled and subjected to docking analysis with the region binding domain (RBD) region of the SARS-CoV-2 Spike protein. The appearance of multiple forms of cathelicidins verifies the complex microbial challenges encountered by these species. Learning more about antiviral defenses of bats and how they drive virus evolution will help scientists to investigate the function of antimicrobial peptides in these species.


Assuntos
Catelicidinas/química , Catelicidinas/farmacologia , Quirópteros/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/química , Antivirais/farmacologia , Sítios de Ligação , Catelicidinas/genética , Catelicidinas/metabolismo , Biologia Computacional/métodos , Simulação por Computador , Genoma , Simulação de Acoplamento Molecular , Filogenia
13.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1167669

RESUMO

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Assuntos
Chicória/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Antivirais/química , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Chicória/fisiologia , Culinária , Hipersensibilidade Alimentar/etiologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Plantas Medicinais/química
14.
Int J Mol Sci ; 22(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920681

RESUMO

Punica granatum L. (pomegranate) fruit is known to be an important source of bioactive phenolic compounds belonging to hydrolysable tannins. Pomegranate extracts have shown antifungal activity, but the compounds responsible for this activity and their mechanism/s of action have not been completely elucidated up to now. The aim of the present study was the investigation of the inhibition ability of a selection of pomegranate phenolic compounds (i.e., punicalagin, punicalin, ellagic acid, gallic acid) on both plant and human fungal pathogens. In addition, the biological target of punicalagin was identified here for the first time. The antifungal activity of pomegranate phenolics was evaluated by means of Agar Disk Diffusion Assay and minimum inhibitory concentration (MIC) evaluation. A chemoinformatic analysis predicted for the first time topoisomerases I and II as potential biological targets of punicalagin, and this prediction was confirmed by in vitro inhibition assays. Concerning phytopathogens, all the tested compounds were effective, often similarly to the fungicide imazalil at the label dose. Particularly, punicalagin showed the lowest MIC for Alternaria alternata and Botrytis cinerea, whereas punicalin was the most active compound in terms of growth control extent. As for human pathogens, punicalagin was the most active compound among the tested ones against Candida albicans reference strains, as well as against the clinically isolates. UHPLC coupled with HRMS indicated that C. albicans, similarly to the phytopathogen Coniella granati, is able to hydrolyze both punicalagin and punicalin as a response to the fungal attack. Punicalagin showed a strong inhibitory activity, with IC50 values of 9.0 and 4.6 µM against C. albicans topoisomerases I and II, respectively. Altogether, the results provide evidence that punicalagin is a valuable candidate to be further exploited as an antifungal agent in particular against human fungal infections.


Assuntos
Antifúngicos/farmacologia , Taninos Hidrolisáveis/farmacologia , Romã (Fruta)/química , Inibidores da Topoisomerase/farmacologia , Antifúngicos/química , Aspergillus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Taninos Hidrolisáveis/química , Inibidores da Topoisomerase/química
15.
Molecules ; 26(9)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33923002

RESUMO

Artemisia abrotanum L. (southern wormwood) is a plant species with an important position in the history of European and Asian medicine. It is a species famous as a medicinal plant in Central Asia, Asia Minor, and in South-East and Central Europe. The raw materials obtained from this species are Abrotani herba and Abrotani folium. In the traditional European medicine, they have been used successfully most of all in liver and biliary tract diseases, in parasitic diseases in children and as antipyretic medication. In the official European medicine, this plant species is recommended by the French Pharmacopoeia for use in homeopathy. In many European countries, it is used traditionally in allopathy. The latest studies on the biological activity of extracts from the aboveground parts of the plant and/or the leaves, and/or the essential oil have provided evidence of other possible applications related to their antibacterial, antifungal, antioxidant, anticancer, and antiallergic properties. The latest studies have also focused on the repellent activity of the essential oil of this species and the possibility to use it in the prevention of diseases in which insects are the vectors. The main substances obtained from the plant that are responsible for this activity are: the essential oil, coumarins, phenolic acids, and flavonoids. Some of the latest investigations emphasize the large differences in the composition of the essential oil, determined by the geographical (climatic) origin of the plant. A. abrotanum is recommended by the European Cosmetic Ingredients Database (CosIng) as a source of valuable cosmetic ingredients. Additionally, the leaves of this species possess a well-established position in the food industry. This plant species is also the object of biotechnological studies.


Assuntos
Antioxidantes/uso terapêutico , Artemisia/química , Medicina Tradicional , Óleos Voláteis/química , Antifúngicos/química , Antifúngicos/uso terapêutico , Antioxidantes/química , Cosméticos , Humanos , Repelentes de Insetos/química , Repelentes de Insetos/uso terapêutico , Óleos Voláteis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química
16.
Molecules ; 26(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33799919

RESUMO

Herein, we investigated the surface characterization and biocompatibility of a denture-lining material containing Cnidium officinale extracts and its antifungal efficacy against Candida albicans. To achieve this, a denture-lining material containing various concentrations of C. officinale extract and a control group without C. officinale extract were prepared. The surface characterization and biocompatibility of the samples were investigated. In addition, the antifungal efficacy of the samples on C. albicans was investigated using spectrophotometric growth and a LIVE/DEAD assay. The results revealed that there was no significant difference between the biocompatibility of the experimental and control groups (p > 0.05). However, there was a significant difference between the antifungal efficiency of the denture material on C. albicans and that of the control group (p < 0.05), which was confirmed by the LIVE/DEAD assay. These results indicate the promising potential of the C. officinale extract-containing denture-lining material as an antifungal dental material.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Cnidium/química , Reembasadores de Dentadura , Extratos Vegetais/farmacologia , Antifúngicos/química , Antifúngicos/toxicidade , Linhagem Celular , Cor , Reembasadores de Dentadura/microbiologia , Fibroblastos/efeitos dos fármacos , Humanos , Teste de Materiais , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Propriedades de Superfície
17.
Molecules ; 26(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800071

RESUMO

Eucalyptus grandis × E. urophylla was a unique hybridization in China. However, the chemical and pharmacological properties were rarely reported. Therefore, in this work, we used a steam distillation method to obtain essential oils from leaves of E. grandis × E. urophylla, and further evaluated the antioxidant, antimicrobial, and phytotoxic potential of the essential oil. Gas chromatography mass spectrometry (GC-MS) was applied to investigate the chemical composition of E. grandis × E. urophylla essential oil (EEO) and the results showed that the main components of EEO were monoterpenes followed by sesquiterpenes. Among them, α-pinene accounted about 17.02%. EEO could also well scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals showing a good free radical clearance ability. In addition, EEO efficiently inhibited the growth of six kinds of bacteria as well as seven kinds of plant pathogens, especially Salmonella typhimurium and Colletotrichum gloeosporioides. Moreover, the seedling germination of Raphanus sativus, Lactuca sativa, Lolium perenne, and Bidens pilosa was significantly suppressed by EEO, thus, indicating essential oils from eucalyptus possessed an excellent phytotoxic activity. This study may give a better understanding on EEO and provide a pharmacological activities analysis contributing to the further research of EEO as a functional drug in agronomic and cosmetic industries.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Óleo de Eucalipto/química , Óleo de Eucalipto/farmacologia , Antibacterianos/química , Antifúngicos/química , Antioxidantes/química , Eucalyptus/química , Óleo de Eucalipto/análise , Óleo de Eucalipto/toxicidade , Cromatografia Gasosa-Espectrometria de Massas , Germinação/efeitos dos fármacos , Alface/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Sementes/efeitos dos fármacos
18.
Int J Mol Sci ; 22(9)2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33922907

RESUMO

Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported.


Assuntos
Antifúngicos/farmacologia , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Farmacorresistência Fúngica/efeitos dos fármacos , Antifúngicos/química , Antifúngicos/uso terapêutico , Azóis/farmacologia , Candida/efeitos dos fármacos , Candidíase/microbiologia , Quimioterapia Combinada , Equinocandinas/farmacologia , Humanos , Micologia/métodos , Polienos/farmacologia , Falha de Tratamento
19.
Molecules ; 26(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919066

RESUMO

This study focuses on the role of photosensitizers in photodynamic therapy. The photosensitizers were prepared in combinations of 110/220 µM erythrosine and/or 10/20 µM demethoxy/bisdemethoxy curcumin with/without 10% (w/w) nano-titanium dioxide. Irradiation was performed with a dental blue light in the 395-480 nm wavelength range, with a power density of 3200 mW/cm2 and yield of 72 J/cm2. The production of ROS and hydroxyl radical was investigated using an electron paramagnetic resonance spectrometer for each individual photosensitizer or in photosensitizer combinations. Subsequently, a PrestoBlue® toxicity test of the gingival fibroblast cells was performed at 6 and 24 h on the eight highest ROS-generating photosensitizers containing curcumin derivatives and erythrosine 220 µM. Finally, the antifungal ability of 22 test photosensitizers, Candida albicans (ATCC 10231), were cultured in biofilm form at 37 °C for 48 h, then the colonies were counted in colony-forming units (CFU/mL) via the drop plate technique, and then the log reduction was calculated. The results showed that at 48 h the test photosensitizers could simultaneously produce both ROS types. All test photosensitizers demonstrated no toxicity on the fibroblast cells. In total, 18 test photosensitizers were able to inhibit Candida albicans similarly to nystatin. Conclusively, 20 µM bisdemethoxy curcumin + 220 µM erythrosine + 10% (w/w) nano-titanium dioxide exerted the highest inhibitory effect on Candida albicans.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Curcumina/química , Curcumina/farmacologia , Eritrosina/química , Fotoquimioterapia , Titânio/química , Antioxidantes/química , Antioxidantes/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Fibroblastos/metabolismo , Gengiva/citologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo
20.
Molecules ; 26(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33800987

RESUMO

Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-ß-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-ß-glucoside (2), stigmasterol-3-O-ß-glucoside (3), pinitol (4), 6ß-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.


Assuntos
Anti-Helmínticos , Antifúngicos , Glicosídeos , Lamiaceae/química , Extratos Vegetais/química , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Ascomicetos/crescimento & desenvolvimento , Botrytis/crescimento & desenvolvimento , Caenorhabditis elegans/crescimento & desenvolvimento , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Phytophthora infestans/crescimento & desenvolvimento
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