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1.
Acta Biochim Pol ; 71: 11999, 2024.
Article in English | MEDLINE | ID: mdl-38721306

ABSTRACT

Candida glabrata is an important opportunistic human pathogen well known to develop resistance to antifungal drugs. Due to their numerous desirable qualities, antimicrobial lipopeptides have gained significant attention as promising candidates for antifungal drugs. In the present study, two bioactive lipopeptides (AF4 and AF5 m/z 1071.5 and 1085.5, respectively), coproduced and purified from Bacillus subtilis RLID12.1, consist of seven amino acid residues with lipid moieties. In our previous studies, the reversed phased-HPLC purified lipopeptides demonstrated broad-spectrum of antifungal activities against over 110 Candida albicans, Candida non-albicans and mycelial fungi. Two lipopeptides triggered membrane permeabilization of C. glabrata cells, as confirmed by propidium iodide-based flow cytometry, with PI uptake up to 99% demonstrating fungicidal effects. Metabolic inactivation in treated cells was confirmed by FUN-1-based confocal microscopy. Together, the results indicate that these lipopeptides have potentials to be developed into a new set of antifungals for combating fungal infections.


Subject(s)
Antifungal Agents , Bacillus subtilis , Candida glabrata , Cell Membrane Permeability , Lipopeptides , Microbial Sensitivity Tests , Lipopeptides/pharmacology , Lipopeptides/chemistry , Lipopeptides/isolation & purification , Bacillus subtilis/drug effects , Candida glabrata/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Cell Membrane Permeability/drug effects , Humans , Cell Membrane/drug effects , Cell Membrane/metabolism
2.
Pak J Pharm Sci ; 37(2): 257-263, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767092

ABSTRACT

The objective of this study was to identify the major compounds present in Cedar tar obtained by distillation of Cedrus atlantica wood from the Taza forest (Morocco) and to evaluate its antidermatophytic activity in vitro against the three strains of dermatophytes most widespread in Morocco, considered the main prevailing causes of fungal infections of the skin, hair and nails. GC/MS analysis revealed that cedar tar is composed mainly of hydrocarbon sesquiterpenes and oxygenated sesquiterpenes, with nine major compounds identified, including α-Cedrene, ß-Cadinene, γ-Cadinene, ß-Himachelene, α-Turmerone, ß-Turmerone, Ar-tumerone, α-Atlantone and Himachalol. The evaluation of antifungal activity was carried out by the micro dilution technique. The MIC values found were 100µg/mL, 2µg/mL and 0.1µg/mL on Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis strains respectively. The observed strong antifungal activity of cedar tar is attributed to the prevalence of oxygenated and hydrocarbon sesquiterpenes, known for their established antidermatophytic properties. This study highlights the potential of the Atlas Cedar tar as an effective antifungal agent for the treatment of superficial mycoses, particularly dermatophytoses.


Subject(s)
Antifungal Agents , Arthrodermataceae , Cedrus , Microbial Sensitivity Tests , Microsporum , Microsporum/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/isolation & purification , Arthrodermataceae/drug effects , Cedrus/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Gas Chromatography-Mass Spectrometry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/analysis , Phytochemicals/chemistry , Morocco
3.
J Chromatogr A ; 1726: 464972, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38744184

ABSTRACT

The effect of internal and external magnetic fields on the separation of antifungal drugs by centrifugal acceleration thin-layer chromatography was reported for the first time. External and internal magnetic fields were applied using neodymium magnets and CoFe2O4@SiO2 ferromagnetic nanoparticles. Separation of ketoconazole and clotrimazole was performed using a mobile phase consisting of n-hexane, ethyl acetate, ethanol, and ammonia (2.0:2.0:0.5:0.2, v/v). The influence of the magnetic field on the entire chromatographic system led to changes in the properties of the stationary and mobile phases and the analytes affecting the retention factor, shape, and width of the separated rings. The extent of this impact depended on the structure of the analyte and the type and intensity of the magnetic field. In the presence of the external magnetic field, there were more significant changes in the chromatographic parameters of the drugs, especially the width of the separated rings, and ketoconazole was more affected than clotrimazole. The changes are conceivably due to the effect of the magnetic field on the analyte distribution between the stationary and mobile phases, which is also caused by the possibility of the magnetic field affecting the viscosity, surface tension, and surface free energy between the stationary and mobile phases.


Subject(s)
Antifungal Agents , Ketoconazole , Magnetic Fields , Chromatography, Thin Layer/methods , Antifungal Agents/analysis , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Ketoconazole/chemistry , Ketoconazole/analysis , Clotrimazole/chemistry , Clotrimazole/analysis , Centrifugation/methods , Silicon Dioxide/chemistry
4.
Chem Biodivers ; 21(5): e202400027, 2024 May.
Article in English | MEDLINE | ID: mdl-38602839

ABSTRACT

Garlic oil has a wide range of biological activities, and its broad-spectrum activity against phytopathogenic fungi still has the potential to be explored. In this study, enzymatic treatment of garlic resulted in an increase of approximately 50 % in the yield of essential oil, a feasible GC-MS analytical program for garlic oil was provided. Vacuum fractionation of the volatile oil and determination of its inhibitory activity against 10 fungi demonstrated that garlic oil has good antifungal activity. The antifungal activity levels were ranked as diallyl trisulfide (S-3)>diallyl disulfide (S-2)>diallyl monosulfide (S-1), with an EC50 value of S-3 against Botrytis cinerea reached 8.16 mg/L. Following the structural modification of compound S-3, a series of derivatives, including compounds S-4~7, were synthesized and screened for their antifungal activity. The findings unequivocally demonstrated that the compound dimethyl trisulfide (S-4) exhibited exceptional antifungal activity. The EC50 of S-4 against Sclerotinia sclerotiorum reached 6.83 mg/L. SEM, In vivo experiments, and changes in mycelial nucleic acids, soluble proteins and soluble sugar leakage further confirmed its antifungal activity. The study indicated that the trisulfide bond structure was the key to good antifungal activity, which can be developed into a new type of green plant-derived fungicide for plant protection.


Subject(s)
Allyl Compounds , Antifungal Agents , Garlic , Microbial Sensitivity Tests , Oils, Volatile , Sulfides , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Oils, Volatile/chemical synthesis , Sulfides/pharmacology , Sulfides/chemistry , Garlic/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Allyl Compounds/pharmacology , Allyl Compounds/chemistry , Allyl Compounds/isolation & purification , Allyl Compounds/chemical synthesis , Distillation , Drug Design , Botrytis/drug effects , Structure-Activity Relationship , Ascomycota/drug effects , Molecular Structure
5.
J Ethnopharmacol ; 330: 118240, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38677574

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.


Subject(s)
Antifungal Agents , Drug Resistance, Multiple, Fungal , Microbial Sensitivity Tests , Plant Extracts , Plant Leaves , Antifungal Agents/pharmacology , Antifungal Agents/isolation & purification , Animals , Plant Extracts/pharmacology , Plant Leaves/chemistry , Candida auris/drug effects , Candida auris/isolation & purification , Fluconazole/pharmacology , Tenebrio , Drug Synergism , Brazil , Candida/drug effects , Cryptococcus neoformans/drug effects
6.
Mar Drugs ; 22(4)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38667806

ABSTRACT

Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 µg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 µg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM.


Subject(s)
Anti-Bacterial Agents , Lactams, Macrocyclic , Microbial Sensitivity Tests , Multigene Family , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Humans , Lactams, Macrocyclic/pharmacology , Lactams, Macrocyclic/chemistry , Lactams, Macrocyclic/isolation & purification , Polyenes/pharmacology , Polyenes/isolation & purification , Polyenes/chemistry , Candida albicans/drug effects , Cell Line, Tumor , Antarctic Regions , Animals , Porifera/microbiology , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification
7.
Mycologia ; 116(3): 355-369, 2024.
Article in English | MEDLINE | ID: mdl-38573188

ABSTRACT

The discovery of bioactive compounds from fungal natural sources holds immense potential for the development of novel therapeutics. The present study investigates the extracts of soil-borne Penicillium notatum and rhizosphere-inhabiting Aspergillus flavus for their antibacterial, antifungal, and cytotoxic potential. Additionally, two compounds were purified using chromatographic and spectroscopic techniques. The results demonstrated that the ethyl acetate fraction of A. flavus exhibited prominent cytotoxic activity against Artemia salina, whereas the ethyl acetate fraction of P. notatum displayed promising antibacterial potential. At dose concentrations of 10, 100, and 1000 µg mL-1, the ethyl acetate fraction of A. flavus showed mortality percentages of 7.6%, 66.4%, and 90%, respectively. The ethyl acetate fraction of P. notatum extract exhibited significant antibacterial activity, forming inhibition zones measuring 41, 38, 34, 34, and 30 mm against B. subtilis, S. flexneri, E. coli, K. pneumoniae, and S. aureus, respectively, at 1000 µg mL-1. At this concentration, inhibition zones of 28, 27, and 15 mm were recorded for P. vulgaris, S. typhi, and X. oryzae. Using bioassay-guided approach, one compound each was purified from the fungal extracts. The initial purification involved mass spectroscopic analysis, followed by structural elucidation using 500 MHz nuclear magnetic resonance (NMR) spectroscopy. Compound 1, derived from A. flavus, was identified as ethyl 2-hydroxy-5,6-dimethyl-4-oxocyclohex-2-ene-1-carboxylate, with a mass of 212, whereas compound 2, isolated from P. notatum, was identified as 3-amino-2-(cyclopenta-2,4-dien-1-ylamino)-8-methoxy-4H-chromen-4-one, with an exact mass of 270. Based on bioassay results, compound 1 was subjected to brine shrimp lethality assay and compound 2 was tested for its antibacterial potential. Compound 1 exhibited 30% lethality against brine shrimp larvae at a concentration of 100 µg mL-1, whereas at 1000 µg mL-1 the mortality increased to 70%. Compound 2 displayed notable antibacterial potential, forming inhibition zones of 30, 24, 19, and 12 mm against S. aureus, E. coli, B. subtilis, and S. flexneri, respectively. In comparison, the standard antibiotic tetracycline produced inhibition zones of 18, 18, 15, and 10 mm against the respective bacterial strains at the same concentration.


Subject(s)
Anti-Bacterial Agents , Artemia , Aspergillus flavus , Penicillium , Soil Microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Artemia/drug effects , Aspergillus flavus/drug effects , Penicillium/chemistry , Penicillium/drug effects , Animals , Microbial Sensitivity Tests , Bacteria/drug effects , Rhizosphere , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification
8.
Phytochemistry ; 222: 114078, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38574958

ABSTRACT

Six undescribed infrequent eremophilane derivatives including diaportheremopholins A - F and its previously undescribed side chain (E)-2-methyloct-2-enoic acid, together with three known compounds (testacein, xestodecalactones B and C), were isolated from the endophytic fungus Diaporthe sp. BCC69512. The chemical structures were determined based on NMR spectroscopic information in conjunction with the evidence from NOESY spectrum, Mosher's application, and chemical reactions for corroborating the absolute configurations. The isolated compounds were evaluated for biological properties such as antimalarial, anti-TB, anti-phytopathogenic fungal, antibacterial activities and for cytotoxicity against malignant (MCF-7 and NCI-H187) and non-malignant (Vero) cells. Diaportheremopholins B (2) and E (5) possessed broad antimicrobial activity against Mycobacterium tuberculosis, Bacillus cereus, Alternaria brassicicola and Colletotrichum acutatum with MICs in a range of 25.0-50.0 µg/mL. Testacein (7) exhibited strong anti-A. brassicicola and anti-C. acutatum activities with equal MIC values of 3.13 µg/mL. Moreover, diaportheremopholin F (6) and compound 8 displayed antitubercular activity with equal MIC values of 50.0 µg/mL. All tested compounds were non-cytotoxic against MCF-7, NCI-H187, and Vero cells, except those compounds 2 and 5-7 exhibited weak cytotoxicity against both malignant and non-malignant cells with IC50 values in a range of 15.5-115.5 µM.


Subject(s)
Alternaria , Ascomycota , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Humans , Ascomycota/chemistry , Chlorocebus aethiops , Alternaria/chemistry , Vero Cells , Mycobacterium tuberculosis/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Bacillus cereus/drug effects , Animals , Molecular Structure , Drug Screening Assays, Antitumor , Colletotrichum/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antimalarials/pharmacology , Antimalarials/chemistry , Antimalarials/isolation & purification , Structure-Activity Relationship , MCF-7 Cells , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Dose-Response Relationship, Drug
9.
Chem Biodivers ; 21(5): e202302112, 2024 May.
Article in English | MEDLINE | ID: mdl-38531073

ABSTRACT

The essential oils of Senecio plants have been used to treat a wide range of ailments. The current study aimed to extract the essential oil of Senecio glaucus obtained from Egypt's Nile delta and determine its chemical profile using GC-MS and NMR analysis. Then, the antimicrobial activity of the oil has been investigated against different fungal and bacterial strains. In addition, its activity as radical scavenger has been evaluated using DPPH, ABTS, and metal chelating techniques. The results revealed the identification of 50 compounds representing 98.80 % of the oil total mass. Sesquiterpenes, including dehydrofukinone (27.15 %) and 4,5-di-epi-aristolochene (10.27 %), as well as monoterpenes, including p-cymene (4.77 %), represented the most predominant constituents. The dehydrofukinone has been isolated and structurally confirmed using 1D and 2D NMR techniques. The oil has showed remarkable antifungal activity against Candida glabrata and C. albicans where the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were 3.13 µg/mL and 1.50 µg/mL and 12.50 µg/mL and 6.30 µg/mL, respectively that could be attributed to the sesquiterpene ketones present in the aerial tissues of the plant. Also, this oil inhibited the growth of the tested bacteria with MIC ranging from 12.50-100.00 µg/mL. In comparison to ascorbic acid and Trolox, the EO had remarkable scavenging activity of DPPH, ABTS and metal chelating with IC50 values of 313.17±13.4, 493.83±20.1, and 409.13±16.7 µg/mL. The docking studies of the identified compounds of the oil to different microbial targets, including Gyrase B and α-sterol demethylase, showed that the phytol possessed the best binding affinities toward the active sites of both enzymes with ΔG=-7.42 and -7.78 kcal/mol, respectively. In addition, the phytol revealed the highest binding affinity to tyrosine kinase Hck with ΔG=-7.44 kcal/mol.


Subject(s)
Antioxidants , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Senecio , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Senecio/chemistry , Bacteria/drug effects , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Fungi/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Picrates/antagonists & inhibitors , Odorants/analysis , Biphenyl Compounds/antagonists & inhibitors
10.
Chem Biodivers ; 21(5): e202400337, 2024 May.
Article in English | MEDLINE | ID: mdl-38470409

ABSTRACT

Rice sheath blight (RSB), caused by Rhizoctonia solani, is a significant disease of rice. The negative effects of chemical fungicides have created an urgent need for low-toxicity botanical fungicides. Our previous research revealed that the ethanol crude extract of Moutan Cortex (MC) exhibited superior antifungal activity against R. solani at 1000 µg/mL, resulting in a 100 % inhibition rate. The antifungal properties were mainly found in the petroleum ether extract. However, the active ingredients of the extract are still unclear. In this study, gas chromatography-mass spectrometry (GC-MS) was utilised for the analysis of its chemical components. The mycelium growth rate method was utilized to detect the antifungal activity. The findings indicated that paeonol constituted the primary active component, with a content of more than 96 %. Meanwhile, paeonol was the most significant antifungal active ingredient, the antifungal activity of paeonol (EC50=44.83 µg/mL) was much higher than that of ß-sitosterol and ethyl propionate against R. solani. Observation under an optical microscope revealed that paeonol resulted in abnormal mycelial morphology. This study provided theoretical support for identifying monomer antifungal compounds and developing biological fungicides for R. solani.


Subject(s)
Antifungal Agents , Microbial Sensitivity Tests , Paeonia , Rhizoctonia , Rhizoctonia/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Paeonia/chemistry , Acetophenones/pharmacology , Acetophenones/chemistry , Acetophenones/isolation & purification , Gas Chromatography-Mass Spectrometry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Dose-Response Relationship, Drug
11.
Chem Biodivers ; 21(5): e202400090, 2024 May.
Article in English | MEDLINE | ID: mdl-38486477

ABSTRACT

Streptomide (1), a new amide analogue, streptomynone (2), a new quinolinone, and ten known compounds including three aliphatic acids (3-5), two amides (6-7), four cyclic dipeptides (8-11), and an adenosine (12) were isolated from the fermentation broth of Streptomyces sp. YIM S01983 isolated from a sediment sample collected in Bendong Village, Huadong Town, Chuxiong, China. Their structures were determined by analysis of the 1D/2D-NMR and HR-ESI-MS spectra. Compound 12 presented weak antimicrobial activities against Candida albicans and Aligenes faecalis (MIC=64 µg/mL). Compounds 7 and 12 showed weak cytotoxic activity against MHCC97H.


Subject(s)
Amides , Candida albicans , Microbial Sensitivity Tests , Quinolones , Streptomyces , Streptomyces/chemistry , Streptomyces/metabolism , Amides/chemistry , Amides/pharmacology , Amides/isolation & purification , Candida albicans/drug effects , Quinolones/chemistry , Quinolones/pharmacology , Quinolones/isolation & purification , Humans , Cell Line, Tumor , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Enterococcus faecalis/drug effects , Molecular Structure , Structure-Activity Relationship , Drug Screening Assays, Antitumor
12.
J Nat Prod ; 87(4): 705-712, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38547118

ABSTRACT

Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 µg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.


Subject(s)
Antifungal Agents , Citrinin , Colletotrichum , Penicillium , Quinolones , Penicillium/chemistry , Colletotrichum/drug effects , Quinolones/pharmacology , Quinolones/chemistry , Quinolones/isolation & purification , Molecular Structure , Animals , Citrinin/pharmacology , Citrinin/chemistry , Citrinin/isolation & purification , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Microbial Sensitivity Tests
13.
Chem Biodivers ; 21(5): e202302115, 2024 May.
Article in English | MEDLINE | ID: mdl-38415904

ABSTRACT

There is a burgeoning focus on utilizing the antifungal and antioxidant properties of essential oils derived from various plants as a modern and natural approach to combat the growth of fungi that contaminate food. In this study, we used essential oils extracted from Thymus daenensis Celak. subsp. daenensis to address three mycotoxin-producing species of Aspergillus, specifically A. flavus, A. parasiticus, and A. niger, all of which are recognized contaminants of food and agricultural products. Concurrently, the antioxidant properties of the essential oils were evaluated, revealing their noteworthy role in the antifungal activity. Essential oils were derived from T. daenensis subsp. daenensis was observed to have a significant inhibitory effect on all three species of Aspergillus, as evidenced by the minimum inhibitory concentration (MIC) ranging from 575 to 707 ppm and the half-maximal inhibitory concentration (IC50) ranging from 237 to 280 ppm. These results confirm the strong antifungal activity of the essential oils. Furthermore, the essential oil exhibited free radical scavenging activity, resulting in an EC50 value of 37.1 µg/ml. In summary, T. daenensis subsp. daenensis essential oil demonstrated a competitive advantage over other similar plants and synthetic antibiotics. This indicates the promising potential of this essential oil as a natural antifungal agent to control Aspergillus growth and mycotoxin contamination. It offers an alternative or complementary approach to conventional antifungal agents and could be a valuable addition to the arsenal of natural remedies to address fungal contamination in food and agricultural products.


Subject(s)
Antifungal Agents , Aspergillus , Free Radical Scavengers , Microbial Sensitivity Tests , Oils, Volatile , Thymol , Thymus Plant , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Aspergillus/drug effects , Aspergillus/chemistry , Thymus Plant/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Thymol/pharmacology , Thymol/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry , Monoterpenes/isolation & purification
14.
Biochimie ; 220: 167-178, 2024 May.
Article in English | MEDLINE | ID: mdl-38158037

ABSTRACT

Candida albicans and C. glabrata express exporters of the ATP-binding cassette (ABC) superfamily and address them to their plasma membrane to expel azole antifungals, which cancels out their action and allows the yeast to become multidrug resistant (MDR). In a way to understand this mechanism of defense, we describe the purification and characterization of Cdr1, the membrane ABC exporter mainly responsible for such phenotype in both species. Cdr1 proteins were functionally expressed in the baker yeast, tagged at their C-terminal end with either a His-tag for the glabrata version, cgCdr1-His, or a green fluorescent protein (GFP) preceded by a proteolytic cleavage site for the albicans version, caCdr1-P-GFP. A membrane Cdr1-enriched fraction was then prepared to assay several detergents and stabilizers, probing their level of extraction and the ATPase activity of the proteins as a functional marker. Immobilized metal-affinity and size-exclusion chromatographies (IMAC, SEC) were then carried out to isolate homogenous samples. Overall, our data show that although topologically and phylogenetically close, both proteins display quite distinct behaviors during the extraction and purification steps, and qualify cgCdr1 as a good candidate to characterize this type of proteins for developing future inhibitors of their azole antifungal efflux activity.


Subject(s)
Antifungal Agents , Azoles , Candida albicans , Drug Resistance, Fungal , Fungal Proteins , Membrane Transport Proteins , Azoles/pharmacology , Azoles/chemistry , Azoles/metabolism , Fungal Proteins/chemistry , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/isolation & purification , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Candida albicans/drug effects , Membrane Transport Proteins/metabolism , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/genetics , Candida glabrata/drug effects , Candida glabrata/genetics , Candida glabrata/metabolism , ATP-Binding Cassette Transporters/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/chemistry
15.
J Nat Prod ; 85(11): 2620-2625, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36318598

ABSTRACT

We report the discovery of talaropeptins A (1) and B (2), tripeptides with an unusual 5/6/5 heterocyclic scaffold and an N-trans-cinnamoyl moiety, which were identified from the marine-derived fungus Talaromyces purpureogenus CX11. A bioinformatic analysis of the genome of T. purpureogenus CX11 and gene inactivation revealed that the biosynthesis of talaropeptins involves a nonribosomal peptide synthase gene cluster. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 1 and 2 were established by electronic circular dichroism calculations and Marfey's method. The plausible biosynthesis of 1 and 2 is also proposed on the basis of gene deletion, substrate feeding, and heterologous expression. Compounds 1 and 2 showed moderate antifungal activity against phytopathogenic fungus Fusarium oxysporum with MIC values of 12.5 and 25 µg/mL, respectively.


Subject(s)
Antifungal Agents , Oligopeptides , Talaromyces , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Circular Dichroism , Magnetic Resonance Spectroscopy , Molecular Structure , Talaromyces/chemistry , Oligopeptides/chemistry , Oligopeptides/isolation & purification , Oligopeptides/pharmacology
16.
Mar Drugs ; 20(3)2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35323494

ABSTRACT

Six new ß-resorcylic acid derivatives (1-5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported ß-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination of spectroscopic data and chemical reactions. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR data. Notably, compounds 1-3 had a ß-resorcylic acid harboring a long unesterified aliphatic side chain, whereas the long aliphatic chains were esterified to form macrolactones in 4-9. Among the isolated compounds, monocillin I and radicicol showed potent antifungal activities against Cryptococcus neoformans, comparable to clinically available antifungal agents and radicicol showed weak antifungal activity against Candida albicans. These findings provide insight into the chemical diversity of fungal RAL-type compounds and their pharmacological potential.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Chenopodiaceae/microbiology , Colletotrichum/chemistry , Cryptococcus neoformans/drug effects , Hydroxybenzoates/pharmacology , Salt-Tolerant Plants/microbiology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Candida albicans/growth & development , Cryptococcus neoformans/growth & development , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , Molecular Structure , Stereoisomerism
17.
Mar Drugs ; 20(3)2022 Mar 20.
Article in English | MEDLINE | ID: mdl-35323514

ABSTRACT

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of -8.8, -8.6, -9.8, -11.4, -8.0, -11.4, and -9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.


Subject(s)
Antifungal Agents , Biological Products , COVID-19 Drug Treatment , Mucormycosis/drug therapy , Porifera/chemistry , SARS-CoV-2 , Animals , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacokinetics , Antifungal Agents/toxicity , Biological Products/chemistry , Biological Products/isolation & purification , Biological Products/pharmacokinetics , Biological Products/toxicity , COVID-19/complications , Coinfection , Fungal Proteins/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Mucormycosis/etiology , Toxicity Tests, Acute
18.
Mar Drugs ; 20(2)2022 Feb 13.
Article in English | MEDLINE | ID: mdl-35200667

ABSTRACT

Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 µM) and weak (IC50 = 190.45 µM) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C2-carbon-utilizing conditions.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Isocitrate Lyase/drug effects , Streptomyces/metabolism , Antifungal Agents/isolation & purification , Candida albicans/enzymology , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Nitrogen/metabolism
19.
Molecules ; 27(3)2022 Feb 08.
Article in English | MEDLINE | ID: mdl-35164402

ABSTRACT

This study investigated the chemical composition, antioxidant and antimicrobial activity of essential oil extracted from Artemisia aragonensis Lam. (EOA). Hydrodistillation was employed to extract EOA. Gas chromatography with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry analyses (GC-MS) were used to determine the phytochemical composition of EOA. Antioxidant potential was examined in vitro by use of three tests: 2.2-diphenyl-1-picrilhidrazil (DPPH), ferric reducing activity power (FRAP) and total antioxidant capacity assay (TAC). Agar diffusion and microdilution bioassays were used to assess antimicrobial activity. GC/MS and GC-FID detected 34 constituents in the studied EOA. The major component was Camphor (24.97%) followed by Borneol (13.20%), 1,8 Cineol (10.88%), and Artemisia alcohol (10.20%). EOA exhibited significant antioxidant activity as measured by DPPH and FRAP assays, with IC50 and EC50 values of 0.034 ± 0.004 and 0.118 ± 0.008 mg/mL, respectively. EOA exhibited total antioxidant capacity of 7.299 ± 1.774 mg EAA/g. EOA exhibited potent antibacterial activity as judged by the low minimum inhibitory concentration (MIC) values against selected clinically-important pathogenic bacteria. MIC values of 6.568 ± 1.033, 5.971 ± 1.033, 7.164 ± 0.0 and 5.375 ± 0.0 µg/mL were observed against S. aureus, B. subtills, E. coli 97 and E. coli 57, respectively. EOA displayed significant antifungal activity against four strains of fungi: F. oxysporum, C. albicans, A. flavus and A. niger with values of 21.50 ± 0.43, 5.31 ± 0.10, 21.50 ± 0.46 and 5.30 ± 0.036 µg/mL, respectively. The results of the current study highlight the importance of EOA as an alternative source of natural antioxidant and antibacterial drugs to combat antibiotic-resistant microbes and free radicals implicated in the inflammatory responses accompanying microbial infection.


Subject(s)
Anti-Bacterial Agents/chemistry , Antifungal Agents/chemistry , Antioxidants/chemistry , Artemisia/chemistry , Oils, Volatile/chemistry , Phytochemicals/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Drug Resistance, Microbial , Fungi/drug effects , Humans , Microbial Sensitivity Tests , Mycoses/drug therapy , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/pharmacology
20.
Molecules ; 27(2)2022 01 10.
Article in English | MEDLINE | ID: mdl-35056749

ABSTRACT

Five new dimer compounds, namely Taiwaniacryptodimers A-E (1-5), were isolated from the methanol extract of the roots of Taiwania cryptomerioides. Their structures were established by mean of spectroscopic analysis and comparison of NMR data with those of known analogues. Their antifungal activities were also evaluated. Our results indicated that metabolites 1, 2, 4, and 5 displayed moderate antifungal activities against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae.


Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Cupressaceae/chemistry , Plant Roots/chemistry , Antifungal Agents/isolation & purification , Aspergillus niger/drug effects , Candida albicans/drug effects , Dimerization , Drug Evaluation, Preclinical , Magnetic Resonance Spectroscopy , Methanol/chemistry , Microbial Sensitivity Tests , Molecular Structure , Penicillium/drug effects , Plant Extracts/chemistry
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