Fungistatic Activity of Kojic Acid Against Human Pathogenic Fungi and Inhibition of Melanin-production inCryptococcus neoformans

Mycobiology ◽  
2003 ◽  
Vol 31 (4) ◽  
pp. 248 ◽  
Author(s):  
Hee Youn Chee ◽  
Eun Hee Lee
Keyword(s):  
Kojic Acid ◽  
Pathogenic Fungi ◽  
Melanin Production ◽  
Fungistatic Activity

scholarly journals The Organogermanium Compound THGP Suppresses Melanin Synthesis via Complex Formation with L-DOPA on Mushroom Tyrosinase and in B16 4A5 Melanoma Cells

2019 ◽  
Vol 20 (19) ◽  
pp. 4785
Author(s):  
Junya Azumi ◽  
Tomoya Takeda ◽  
Yasuhiro Shimada ◽  
Hisashi Aso ◽  
Takashi Nakamura
Keyword(s):  
Gene Expression ◽  
Kojic Acid ◽  
Biological Activities ◽  
Melanoma Cells ◽  
Tyrosinase Activity ◽  
Melanin Synthesis ◽  
Mushroom Tyrosinase ◽  
Melanin Production ◽  
Organogermanium Compound ◽  
Or Gene

The organogermanium compound 3-(trihydroxygermyl)propanoic acid (THGP) has various biological activities. We previously reported that THGP forms a complex with cis-diol structures. L-3,4-Dihydroxyphenylalanine (L-DOPA), a precursor of melanin, contains a cis-diol structure in its catechol skeleton, and excessive melanin production causes skin darkening and staining. Thus, the cosmetic field is investigating substances that suppress melanin production. In this study, we investigated whether THGP inhibits melanin synthesis via the formation of a complex with L-DOPA using mushroom tyrosinase and B16 4A5 melanoma cells. The ability of THGP to interact with L-DOPA was analyzed by 1H-NMR, and the influence of THGP and/or kojic acid on melanin synthesis was investigated. We also examined the effect of THGP on cytotoxicity, tyrosinase activity, and gene expression and found that THGP interacted with L-DOPA, a precursor of melanin with a cis-diol structure. The results also showed that THGP inhibited melanin synthesis, exerted a synergistic effect with kojic acid, and did not affect tyrosinase activity or gene expression. These results suggest that THGP is a useful substrate that functions as an inhibitor of melanogenesis and that its effect is enhanced by combination with kojic acid.

scholarly journals Virtual Screening of Selected Natural Products as Human Tyrosinase-Related Protein 1 Blockers

2021 ◽  
Author(s):  
Chidi Duru ◽  
Ijeoma Duru ◽  
Chiagoziem Chidiebere
Keyword(s):  
Ascorbic Acid ◽  
Natural Products ◽  
Kojic Acid ◽  
Binding Pocket ◽  
Related Protein ◽  
Melanin Production ◽  
Synthetic Compound ◽  
Skin Lightening ◽  
Tyrosinase Related Protein ◽  
Human Tyrosinase

Many researchers have widely explored the need to replace the harmful compound hydroquinone in skin-lightening creams with more skin-friendly compounds that can give similar results. Some compounds from the plant kingdom have been shown to possess human tyrosinase inhibitory action with no adverse effect on the skin. In this study, the virtual screen of glabridin, kojic acid, arbutin, niacinamide, ascorbic acid, salicin, lactic acid, glutathione, azelaic acid, linoleic acid, glycolic acid, acclaimed to possess this activity as well as the synthetic compound hydroquinone, as human tyrosinase-related protein 1 inhibitor was investigated using computational methods. Site-directed docking was performed at the binding pocket on the enzyme carrying the cocrystallized ligand tropolone. The binding affinity of salicin (-6.7 kcal/mol), a-arbutin (-6.3 kcal/mol), glutathione (-6.2 kcal/mol), ascorbic acid (-5.7 kcal/mol), and niacinamide (-5.7 kcal/mol) were higher than that of the cocrystallized ligand tropolone (-5.5 kcal/mol) and the synthetic skin lightening compound hydroquinone (-4.8 kcal/mol). a-arbutin and glutathione also interacted with similar amino acids units as hydroquinone, suggesting that they followed the exact mechanism of action. These findings strongly corroborate the claim that these natural products could inhibit melanin production and may serve to replace hydroquinone in skin lightening creams.

scholarly journals Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis

2020 ◽  
Vol 477 (13) ◽  
pp. 2489-2507
Author(s):  
Sameh S. M. Soliman ◽  
Rania Hamdy ◽  
Samia A. Elseginy ◽  
Teclegiorgis Gebremariam ◽  
Alshaimaa M. Hamoda ◽  
...  
Keyword(s):  
Natural Product ◽  
Mammalian Cells ◽  
Kojic Acid ◽  
Selective Inhibition ◽  
Positive Control ◽  
Significant Inhibition ◽  
Putative Virulence Factor ◽  
Melanin Production ◽  
Fungal Melanin ◽  
Immunocompetent Mice

Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Herein, we have developed a series of compounds (UOSC-1–14) to selectively target Rhizopus melanin and explored this mechanism therapeutically. The compounds were designed based on the scaffold of the natural product, cuminaldehyde, identified from plant sources and has been shown to develop non-selective inhibition of melanin production. While all synthesized compounds showed significant inhibition of Rhizopus melanin production and limited toxicity to mammalian cells, only four compounds (UOSC-1, 2, 13, and 14) were selected as promising candidates based on their selective inhibition to fungal melanin. The activity of compound UOSC-2 was comparable to the positive control kojic acid. The selected candidates showed significant inhibition of Rhizopus melanin but not human melanin by targeting the fungal tyrosinase, and with an IC50 that are 9 times lower than the reference standard, kojic acid. Furthermore, the produced white spores were phagocytized easily and cleared faster from the lungs of infected immunocompetent mice and from the human macrophages when compared with wild-type spores. Collectively, the results suggested that the newly designed derivatives, particularly UOSC-2 can serve as promising candidate to overcome persistence mechanisms of fungal melanin production and hence make them accessible to host defenses.

scholarly journals Compost bacteria as potential agents in biological plant control

2021 ◽  
Vol 61 (4) ◽  
pp. 319-326
Keyword(s):  
Pathogenic Fungi ◽  
16S Rrna Gene Sequencing ◽  
Alcaligenes Faecalis ◽  
Diffusion Method ◽  
Rrna Gene ◽  
Bacterial Strains ◽  
Fungistatic Activity ◽  
Activity Spectrum ◽  
Rrna Gene Sequencing

The assumptions of integrated pest management put great emphasis on the development of non-chemical methods which increases the interest in biological methods and the search for microorganisms that would be an alternative to the most frequently used fungicides. The aim of the experiments was the isolation of the compost bacteria, in vitro determination of their fungistatic activity against some pathogenic fungi of the genus Fusarium, Alternaria, Sclerotinia, Botrytis, Rhizoctonia and Pythium and identification of selected isolates. From the backyard compost, 44 bacterial strains were isolated and assessed for the fungistatic properties by the well diffusion method. The obtained results allowed for the selection of 12 isolates of compost bacteria, characterised by the broadest and the strongest fungistatic activity spectrum against tested fungi. Identification of bacterial isolates by: MALDI-TOF mass spectrometry and 16S rRNA gene sequencing methods showed their belonging to the species Bacillus subtilis, Alcaligenes faecalis, Stenotrophomonas maltophilia and Serratia liquefaciens.

Synthesis and Cytotoxic Evaluation of Kojic Acid Derivatives with Inhibitory Activity on Melanogenesis in Human Melanoma Cells

2019 ◽  
Vol 18 (15) ◽  
pp. 2137-2148 ◽  
Author(s):  
Gulsah Karakaya ◽  
Ayse Ercan ◽  
Selin Oncul ◽  
Mutlu D. Aytemir
Keyword(s):  
Malignant Melanoma ◽  
Cell Lines ◽  
Kojic Acid ◽  
Mannich Bases ◽  
Melanoma Cells ◽  
Cytotoxic Action ◽  
Melanin Production ◽  
Human Malignant Melanoma ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: Malignant melanoma is an agressive tumour related to the overproduction of melanin, which provides colors of skin, eyes and hair. In addition contributing to the risk of malignant melanoma, abnormal production of melanin has many drawbacks, including hyperpigmentation, post-inflammatory pigmentation, melasma and skin aging. Kojic acid is currently employed in order to lighten skin pigmentation and provide depigmentation. Objective: Mannich bases of kojic acid with the structure of 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/ methyl/morpholinomethyl/piperidinylmethyl/pyrrolidinylmethyl-4H-pyran-4-one (compounds 1-23) were synthesized by the reaction of kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in the presence of formaline. To obtain the cyclic amine (morpholine, piperidine and pyrrolidine) derivatives, nucleophilic substitutions were carried out. Method: Cytotoxic effects on A375 human malignant melanoma, HGF-1 human gingival fibroblasts, and MRC-5 human lung cell lines were investigated by sulphorhodamine B assay. Control agents were vemurafenib, dacarbazine, temozolomide, and lenalidomide, which are the commercially available drugs for the treatment of malignant melanoma. Results: Cytotoxic action against melanoma cells was significantly more efficacious (IC50: 11.26-68.58 μM) than the FDA-approved drugs except for vemurafenib. Fourteen of the compounds were proven to have higher IC50 values for the non-cancerous cell lines, HGF-1, and MRC-5 cells. Melanogenesis inhibition assay was performed to observe the ability of the drugs to inhibit melanin production and certain compounds were shown to be capable of actively inhibiting melanin production in melanoma cells. Conclusion: Mannich bases of kojic acid derivatives may be promising therapeutic agents, since some have more potent effects on melanoma cells than previously FDA-approved drugs for the treatment of malignant melanoma.

scholarly journals Evaluation and Optimization of the Anti-Melanogenic Activity of 1-(2-Cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1372 ◽  
Author(s):  
Byung-Hak Kim ◽  
Soo-Nam Hong ◽  
Sang-Kyu Ye ◽  
Jung-Youl Park
Keyword(s):  
Transcriptional Activity ◽  
Kojic Acid ◽  
Biologically Active ◽  
Melanin Production ◽  
Lead Compounds ◽  
B16f10 Cells ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Derivatives Of ◽  
Expression And Activity

The chemical modification and optimization of biologically active compounds are essential steps in the identification of promising lead compounds for drug development. We previously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives of chalcone 21 and evaluated their anti-melanogenic activity in -MSH-induced B16F10 cells. (E)-N-(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) exhibited the strongest inhibition of cellular melanin production, with an IC50 value of 0.54 M. It was more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin, whose IC50 values were 4.9, 38.5, and 148.4 M, respectively. Chalcone 21-21 decreased the expression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF, the phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our results demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic activity.

scholarly journals Gene cluster conservation identifies melanin and perylenequinone biosynthesis pathways in multiple plant pathogenic fungi

2018 ◽  
Author(s):  
Malaika K. Ebert ◽  
Rebecca E. Spanner ◽  
Ronnie de Jonge ◽  
David J. Smith ◽  
Jason Holthusen ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Plant Pathogens ◽  
Phylogenetic Analyses ◽  
Pathogenic Fungi ◽  
Gene Clusters ◽  
Host Cells ◽  
Plant Pathogenic Fungi ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Melanin Production

SummaryPerylenequinones are a family of structurally related polyketide fungal toxins with nearly universal toxicity. These photosensitizing compounds absorb light energy which enables them to generate reactive oxygen species that damage host cells. This potent mechanism serves as an effective weapon for plant pathogens in disease establishment. The sugar beet pathogenCercospora beticolasecretes the perylenequinone cercosporin during infection. We have shown recently that the cercosporin toxin biosynthesis(CTB)gene cluster is present in several other phytopathogenic fungi, prompting the search for biosynthetic gene clusters (BGCs) of structurally similar perylenequinones in other fungi. Here, we report the identification of the elsinochrome and phleichrome BGCs ofElsinoё fawcettiiandCladosporium phlei,respectively, based on gene cluster conservation with theCTBand hypocrellin BGCs. Furthermore, we show that previously reported BGCs for elsinochrome and phleichrome are involved in melanin production. Phylogenetic analysis of the corresponding melanin polyketide synthases (PKSs) and alignment of melanin BGCs revealed high conservation between the established and newly identifiedC. beticola, E. fawcettii,andC. phleimelanin BGCs. Mutagenesis of the identified perylenequinone and melanin PKSs inC. beticolaandE. fawcettiicoupled with mass spectrometric metabolite analyses confirmed their roles in toxin and melanin production.Originality and significance statementGenes involved in secondary metabolite (SM) production are often clustered together to form biosynthetic pathways. These pathways frequently have highly conserved keystone enzymes which can complicate allocation of a biosynthetic gene cluster (BGC) to the cognate SM. In our study, we utilized a combination of comparative genomics, phylogenetic analyses and biochemical approaches to reliably identify BGCs for perylenequinone toxins and DHN-melanin in multiple plant pathogenic fungi. Furthermore, we show that earlier studies that aimed to identify these perylenequinone pathways were misdirected and actually reported DHN-melanin biosynthetic pathways. Our study outlines a reliable approach to successfully identify fungal SM pathways.

scholarly journals Cryptococcus neoformans Virulence Attributes can be Modulated by Sound Stress

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Kellysson GB Mendes ◽  
◽  
Fabiana Brandao AS ◽  
Raul Alberto Laumann ◽  
Simoni Campos Dias ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Morphological Changes ◽  
Noise Pollution ◽  
Pathogenic Fungi ◽  
Slight Reduction ◽  
Sound Waves ◽  
Melanin Production ◽  
Viable Cells ◽  
Almost All ◽  
The Impact

Sound waves are a prime component making up the environment, and they are present in almost all niches on the planet. In times of increasing noise pollution, the effect of sound stress on humans, animals, and microorganisms is well known. However, the possibility of this kind of pressure in the environment, affecting pathogenic fungi, which live in the background as saprophytes, has not been explored. Fungi can develop attributes and become virulent due to adaptation to selective pressure or stress. In this context, our group has become interested in evaluating the impact of sound stress on the fungus Cryptococcus neoformans, a pathogen that has high phenotypic plasticity. C. neoformans strain H99 was chosen for all assays. The yeasts were cultivated at 30°C, exposed or not to the frequency of 8 kHz. We observed morphological changes in these cells, such as the expression of phenotype virulence attributes: capsule expansion and melanin production. We also analyzed the number of viable cells after exposure, and we observed the yeast’s susceptibility to antifungals. After the treatment with 8 kHz, the cells showed a significant increase in the capsule expansion, an acceleration of the melanin production, and a slight reduction in the number of viable cells. Finally, tests performed with the antifungals showed a decrease in inhibition halo on the plate test. Our results are innovative and suggest that stress caused by sound could incite increased virulence in this fungus.

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