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1.
Microb Cell Fact ; 23(1): 68, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408972

RESUMO

Owing to the growing need for natural materials in different fields, studying melanin production from biological sources is imperative. In the current study, the extracellular melanin pigment was produced by the fungus Curvularia soli AS21 ON076460. The factors that affect the production of melanin were optimized by the Plackett-Burman design (P-BD). The effect of gamma irradiation on melanin productivity was investigated. The maximum melanin yield (3.376 mg/L) was elicited by a stimulus of gamma irradiation at 1.0 kGy. The results evoked that, Curvularia soli AS21 ON076460 melanin exhibited excellent antimicrobial activity against all tested bacteria and fungi. Klebsiella pneumoniae ATCC 13883 and P. digitatum were mostly affected by melanin registering the inhibition zone diameters of 37.51 ± 0.012 and 44.25 ± 0.214 mm, respectively. Moreover, Curvularia soli AS21 ON076460 melanin indicated a significant antiviral efficacy (77% inhibition) of Herpes simplex virus (HSV1). The melanin pigment showed antioxidant activities with IC50 of 42 ± 0.021 and 17 ± 0.02 µg/mL against DPPH and NO, respectively. Melanin had cytotoxic action against human breast cancer and skin cancer cell lines (Mcf7and A431) as well as exerting a low percentage of cell death against normal skin cell lines (Hfb4). Melanin was effective in wound management of human skin cells by 63.04 ± 1.83% compared with control (68.67 ± 1.10%). The novelty in the study is attributed to the possibility of using gamma rays as a safe method in small economic doses to stimulate melanin production from the fungi that have been isolated. In summary, melanin produced from fungi has significant biological activities that encourage its usage as a supportive medical route.


Assuntos
Fungos , Melaninas , Humanos , Raios gama , Fungos/metabolismo , Curvularia/metabolismo
2.
J Am Chem Soc ; 143(7): 2970-2983, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33570388

RESUMO

Structurally unprecedented antibacterial alkaloids containing multiple electron-rich pyrrole units have recently been isolated from Curvularia sp. and Bipolaris maydis fungi. This article documents the evolution of a synthetic program aimed at accessing the flagship metabolites curvulamine and curindolizine which are presumably a dimer and trimer of a C10N biosynthetic building block, respectively. Starting with curvulamine, we detail several strategies to merge two simple, bioinspired fragments, which while ultimately unsuccessful, led us toward a pyrroloazepinone building block-based strategy and an improved synthesis of this 10π-aromatic heterocycle. A two-step annulation process was then designed to forge a conserved tetracyclic bis-pyrrole architecture and advanced into a variety of late-stage intermediates; unfortunately, however, a failed decarboxylation thwarted the total synthesis of curvulamine. By tailoring our annulation precursors, success was ultimately found through the use of a cyanohydrin nucleophile which enabled a 10-step total synthesis of curvulamine. Attempts were then made to realize a biomimetic coupling of curvulamine with an additional C10N fragment to arrive at curindolizine, the most complex family member. Although unproductive, we developed a 14-step total synthesis of this alkaloid through an abiotic coupling approach. Throughout this work, effort was made to harness and exploit the innate reactivity of the pyrrole nucleus, an objective which has uncovered many interesting findings in the chemistry of this reactive heterocycle.


Assuntos
Alcaloides/síntese química , Alcaloides Indólicos/síntese química , Alcaloides/química , Azepinas/química , Bipolaris/química , Bipolaris/metabolismo , Cristalografia por Raios X , Curvularia/química , Curvularia/metabolismo , Ciclização , Alcaloides Indólicos/química , Indolizidinas/química , Conformação Molecular , Pirróis/química , Estereoisomerismo
3.
Environ Microbiol ; 23(2): 613-627, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32452607

RESUMO

Iron is virtually an essential nutrient for all organisms, to understand how iron contributes to virulence of plant pathogenic fungi, we identified ClFTR1 and ClNPS6 in maize pathogen Curvularia lunata (Cochliobolus lunatus) in this study. Disruption of ClNPS6 significantly impaired siderophore biosynthesis. ClFTR1 and ClNPS6 did mediate oxidative stress but had no significant impact on vegetative growth, conidiation, cell wall integrity and sexual reproduction. Conidial germination delayed and appressoria formation reduced in ΔClftr1 comparing with wild type (WT) CX-3. Genes responsible for conidial germination, appressoria formation, non-host selective toxin biosynthesis and cell wall degrading enzymes were also downregulated in the transcriptome of ΔClftr1 and ΔClnps6 compared with WT. The conidial development, toxin biosynthesis and polygalacturonase activity were impaired in the mutant strains with ClFTR1 and ClNPS6 deletion during their infection to maize. ClFTR1 and ClNPS6 were upregulated expression at 12-24 and 48-120 hpi in WT respectively. ClFTR1 positively regulated conidial germination, appressoria formation in the biotrophy-specific phase. ClNPS6 positively regulates non-host selective toxin biosynthesis and cell wall degrading enzyme activity in the necrotrophy-specific phase. Our results indicated that ClFTR1 and ClNPS6 were key genes of pathogen known to conidia development and virulence factors.


Assuntos
Curvularia/metabolismo , Curvularia/patogenicidade , Proteínas Fúngicas/metabolismo , Doenças das Plantas/microbiologia , Esporos Fúngicos/crescimento & desenvolvimento , Fatores de Virulência/metabolismo , Zea mays/microbiologia , Parede Celular/genética , Parede Celular/metabolismo , Curvularia/genética , Curvularia/crescimento & desenvolvimento , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Ferro/metabolismo , Reprodução Assexuada , Esporos Fúngicos/genética , Esporos Fúngicos/metabolismo , Esporos Fúngicos/patogenicidade , Virulência , Fatores de Virulência/genética
4.
Mar Drugs ; 18(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143384

RESUMO

A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo2 (OAc)4-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC50 values of 1.3-2.5 µM, and an in silico molecular docking study was also performed.


Assuntos
Benzofuranos/farmacologia , Inibidores da Colinesterase/farmacologia , Curvularia/metabolismo , Éteres de Glicerila/farmacologia , Lipopeptídeos/farmacologia , Células A549 , Acetilcolinesterase/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Benzofuranos/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Éteres de Glicerila/isolamento & purificação , Células HeLa , Humanos , Células K562 , Lipopeptídeos/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
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