Acridone alkaloids as potent inhibitors of cathepsin V

Severino, Richele P.; Güido, Rafael Victório Carvalho; Marques, Emerson Finco; Brὂmme, Dieter; Silva, Maria Fátima das Graças Fernandes da; Fernandes, João B.; Andricopulo, Adriano D.; Vieira, Paulo C.

doi:10.1016/j.bmc.2010.12.056

Cited by 31 publications

(10 citation statements)

References 28 publications

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“…A flavonoid 3′,4′,7,8-tetrahydroxyflavone from Acacia confusa inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation, by lowering the mRNA expression levels of cathepsin K [92]. Acridone alkaloids from Swinglea glutinosa could reversibly inhibit cathepsin V by competitive inhibition [93].…”

Section: Cathepsin Inhibitorsmentioning

confidence: 99%

Cathepsins: Proteases that are vital for survival but can also be fatal

Patel

Homaei

El‐Seedi

et al. 2018

Biomedicine & Pharmacotherapy

146

103

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The state of enzymes in the human body determines the normal physiology or pathology, so all the six classes of enzymes are crucial. Proteases, the hydrolases, can be of several types based on the nucleophilic amino acid or the metal cofactor needed for their activity. Cathepsins are proteases with serine, cysteine, or aspartic acid residues as the nucleophiles, which are vital for digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, among a litany of other functions. But inflammatory state radically affects their normal roles. Released from the lysosomes, they degrade extracellular matrix proteins such as collagen and elastin, mediating parasite infection, autoimmune diseases, tumor metastasis, cardiovascular issues, and neural degeneration, among other health hazards. Over the years, the different types and isoforms of cathepsin, their optimal pH and functions have been studied, yet much information is still elusive. By taming and harnessing cathepsins, by inhibitors and judicious lifestyle, a gamut of malignancies can be resolved. This review discusses these aspects, which can be of clinical relevance.

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Section: Cathepsin Inhibitorsmentioning

confidence: 99%

Cathepsins: Proteases that are vital for survival but can also be fatal

Patel

Homaei

El‐Seedi

et al. 2018

Biomedicine & Pharmacotherapy

146

103

View full text Add to dashboard Cite

show abstract

“…Regarding cathepsin V inhibitors from other natural sources, Severino et al [32] described some promising acridone alkaloids, specifically citibrasine, which exhibited high activity on cathepsin V and was considered a promising lead compound. Later, Sarria et ▶ al.…”

Section: Resultsmentioning

confidence: 99%

“…Cathepsin V inhibition was evaluated in vitro as previously described [32,33]. Briefly, the enzymatic activity was measured by the increase in fluorescence from the hydrolysis of the Z-FR-MCA substrate (Z-Phe-Arg-7-amido-4-methylcoumarin) by cathepsin V, releasing MCA.…”

Section: Bioassay Of Cathepsin V Inhibitionmentioning

confidence: 99%

Liquid Fungal Cocultivation as a Strategy to Access Bioactive Metabolites

et al. 2020

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AbstractFungi are a rich source of bioactive compounds. Fungal cocultivation is a method of potentiating chemical interactions and, consequently, increasing bioactive molecule production. In this study, we evaluated the bactericidal, antiprotozoal, and cathepsin V inhibition activities of extracts from axenic cultures of 6 fungi (Fusarium guttiforme, Pestalotiopsis diospyri, Phoma caricae-papayae, Colletotrichum horii, Phytophthora palmivora, and C. gloeosporioides) that infest tropical fruits and 57 extracts obtained by their cocultivation. Our results reveal that fungal cocultivation enhances the biological activity of the samples, since all extracts that were active on Gram-positive bacteria, Gram-negative bacteria, Trypanosoma cruzi, and Leishmania infantum were obtained from cocultivation. Bacterial growth is either totally or partially inhibited by 46% of the extracts. Two extracts containing mainly fusaric and 9,10-dehydrofusaric acids were particularly active. The presence of the fungus F. guttiforme in co-cultures that give rise to extracts with the highest activities against L. infantum. An axenic culture gave rise to the most active extract for the inhibition of cathepsin V; however, other coculture extracts also exhibited activity toward this biological target. Therefore, the results of the biological activities indicate that fungal cocultivation increased the biological potential of samples, likely due to the hostile and competitive environment that pushes microorganisms to produce substances important for defense and allows access to metabolic routes then silenced in milder cultivation conditions.

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“…San Jose, CA, USA), was used. In addition, IC 50 was determined for compounds with inhibition greater than 60% by rate values using SigmaPlot 12.0 (Systat Software, San Jose, CA, USA) [32,33].…”

Section: Enzymatic Assaysmentioning

confidence: 99%

Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases

et al. 2020

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Papain-like cysteine proteases (PLCPs) in plants are essential to prevent phytopathogen invasion. In order to search for cysteine protease inhibitors and to investigate compounds that could be associated to pineapple Fusarium disease, a chemistry investigation was performed on Fusarium proliferatum isolated from Ananas comosus (pineapple) and cultivated in Czapek medium. From F. proliferatum extracts, nine secondary metabolites were isolated and characterized by nuclear magnetic resonance spectroscopy and mass spectrometry experiments: beauvericin (1), fusaric acid (2), N-ethyl-3-phenylacetamide (3), Nacetyltryptamine (4), cyclo(L-Val-L-Pro) cyclodipeptide (5), cyclo(L-Leu-L-Pro) cyclodipeptide (6), cyclo(L-Leu-L-Pro) diketopiperazine (7), 2,4-dihydroxypyrimidine (8), and 1H-indole-3-carbaldehyde (9). Compounds 1, 3, and 6 showed significant inhibition of papain, with IC 50 values of 25.3 ± 1.9, 39.4 ± 2.5, and 7.4 ± 0.5 μM, respectively. Compound 1 also showed significant inhibition against human cathepsins V and B with IC 50 of 46.0 ± 3.0 and 6.8 ± 0.7 μM, respectively. The inhibition of papain by mycotoxins (fusaric acid and beauvericin) may indicate a mechanism of Fusarium in the roles of infection process.

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Acridone alkaloids as potent inhibitors of cathepsin V

Cited by 31 publications

References 28 publications

Cathepsins: Proteases that are vital for survival but can also be fatal

Cathepsins: Proteases that are vital for survival but can also be fatal

Liquid Fungal Cocultivation as a Strategy to Access Bioactive Metabolites

Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases

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