Antidermatophytic activity of synthetic peptides: Action mechanisms and clinical application as adjuvants to enhance the activity and decrease the toxicity of Griseofulvin

Souza, Pedro F.N.; Lima, Patrícia G.; Freitas, Cléverson D.T.; Sousa, Daniele O.B.; Neto, Nilton A. S.; Dias, Lucas Pinheiro; Vasconcelos, Ilka M.; Freitas, Larissa Barbosa Nogueira; Silva, Rafael G. G.; Sousa, J. S. de; Silva, Ayrles F.B.; Oliveira, José T.A.

doi:10.1111/myc.13138

Cited by 13 publications

(14 citation statements)

References 28 publications

(55 reference statements)

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“…Regarding the antimicrobial potential, Mo -CBP 3 -PepI presents great anticandidal activity against Candida albicans , C. parapsilosis , C. krusei , and C. tropicalis . The mechanisms of action of Mo -CBP3-PepI against the Candida genus were revealed using C. albicans as a model [ 15 , 16 , 17 ]. Regarding the antibacterial activity, Mo -CBP3-PepI, the only relevant activity, was evaluated against K. pneumoniae .…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae

et al. 2022

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Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL−1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics was seen. The reduction in proteins involved in vital processes for cell life, such as DNA repair, cell wall turnover, and protein turnover, results in the accumulation of ROS, driving the cell to death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

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Section: Introductionmentioning

confidence: 99%

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae

et al. 2022

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“…The cell viability assay was performed as described by Lima et al [17], with some adjustments. After the antibacterial assay was done as described by Oliveira et al [15], the wells containing the treated cells and control cells (50 µL) were incubated for 3h in the dark at 37 ºC with 50 µL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (2 mg mL -1 , MTT).…”

Section: Cell Viability By Mtt Assaymentioning

confidence: 99%

“…Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII are synthetic peptides derived from a chitin-binding protein purified from Moringa oleifera [15]. Likewise, Mo-CBP3-PepII and Mo-CBP3-PepIII, Mo-CBP3-PepI to chitin and induce membrane pore in important human pathogenic fungi such as Candida spp., Cryptococcus neoformans, and Trichophyton mentagrophytes [16,17,25]. Here, the bacterial potential and mechanisms of action behind the antibacterial activity of Mo-CBP3-PepI against K. pneumoniae cells are presented for the first time.…”

Section: Membrane Pore Formation and Ros Overproductionmentioning

confidence: 99%

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP<sub>3</sub>-PepI against <em>Klebsiella pneumoniae</em>

Branco¹,

Souza²,

Neto³

et al. 2022

Preprint

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Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, it was seen a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics. These reductions lead to the inhibition of DNA repair, inhibition of cell wall turnover, protein turnover, and ROS accumulation leading to cell death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

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“…d. Griseofulvin mixed with peptides can reduce or eliminate drug toxicity to human erythrocytes 21 .…”

Section: Toxicity Testmentioning

confidence: 99%

Drug Discovery of Griseofulvin : A Review

Jumiati¹,

Chandra²,

Asra³

2021

Asian J Pharm Res Dev

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Background: Griseofulvin is a fungistatic antifungal drug used to treat dermatophytosis. Dermatophytes that are often found include Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum. Purpose: This review article aims to discuss the drug discovery review of griseofulvin. Data Source: The author created this review article using the literature study method relevant to the purpose of the review. Sources of information from national journals and international journals that are accessed through online sites such as Google Scholar, Research Gate, Science Direct, Springer Link, and NCBI. Key words were used to find the journals, namely griseofulvin, dermatophyte, toxicity. Conclusion: The conclusion of this article is that griseofulvin is used as an antifungal drug containing chlorine from Penicillium griseofulvum isolated against mycelium fungus. This drug is non-toxic, so it is effective and safe to fight various types of fungal infections of the skin such as tinea capitis and remains the drug of choice for dermatophytes.

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Antidermatophytic activity of synthetic peptides: Action mechanisms and clinical application as adjuvants to enhance the activity and decrease the toxicity of Griseofulvin

Cited by 13 publications

References 28 publications

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP<sub>3</sub>-PepI against <em>Klebsiella pneumoniae</em>

Drug Discovery of Griseofulvin : A Review

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