Antitumor effect of depsidones from lichens on tumor cell lines and experimental murine melanoma

Alexandrino, Caroline Almeida Farias; Honda, Nobuaki; Matos, Maria de Fátima Cepa; Portugal, Luciane Candeloro; Souza, Pedro Rafael Berquó de; Perdomo, Renata Trentin; Guimarães, Rita de Cássia Avellaneda; Toffoli-Kadri, Mônica Cristina; Silva, Magalli Costa Barbosa Lima; Bogo, Danielle

doi:10.1016/j.bjp.2019.04.005

Cited by 13 publications

(8 citation statements)

References 32 publications

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“…Previous evidence showed that both compounds have antiproliferative effects on a variety of tumoral cellular models, including colorectal and melanoma cancer cell lines. In contrast, no adverse effects were detected on normal cell culture [52][53][54][55][56]. In line with this, our results confirmed the absence of any significant cytotoxic effect for both compounds up to 48 h of exposure at the tested doses.…”

Section: Discussionsupporting

confidence: 87%

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

et al. 2022

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The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CLpro. The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was performed to ascertain the nature of the binding with the 3CLpro. The compounds are slow-binding inactivators of 3CLpro with a Ki of 3.95 μM and 3.77 μM for protocetraric and salazinic acid, respectively, and inhibitory efficiency kinact/Ki at about 3 × 10−5 s−1µM−1. The mechanism of inhibition shows that both compounds act as competitive inhibitors with the formation of a stable covalent adduct. The viability assay on epithelial cells revealed that none of them shows cytotoxicity up to 80 μM, which is well below the Ki values. By molecular modelling, we predicted that the catalytic Cys145 makes a nucleophilic attack on the carbonyl carbon of the cyclic ester common to both inhibitors, forming a stably acyl-enzyme complex. The computational and kinetic analyses confirm the formation of a stable acyl-enzyme complex with 3CLpro. The results obtained enrich the knowledge of the already numerous biological activities exhibited by lichen secondary metabolites, paving the way for developing promising scaffolds for the design of cysteine enzyme inhibitors.

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Section: Discussionsupporting

confidence: 87%

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

et al. 2022

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“…Their biological potential is attributed largely to lipophilic phenolic compounds, namely salazinic acid, evernic acid, and (−) -usnic acid, respectively [5,6]. The cytotoxic properties of salazinic acid and P. sulcata extracts, as well as evernic acid and E. prunastri lipophilic extracts, have been confirmed on various cancer cell lines [7][8][9][10]. Moreover, moderate antioxidant activity of salazinic acid [11] and P. sulcata extracts [10,12] has been reported.…”

Section: Introductionmentioning

confidence: 96%

Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties

et al. 2021

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Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (−)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e., cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (−)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (−)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM.

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“…It was found that salazinic acid caused a cell cycle arrest in the sub-G1 apoptotic phase [102]. The group of Alexandrino et al, 2019, also made cytotoxicity tests with salazinic acid, and in their in vitro assays, it was found that the metabolite had a significant anti-proliferative activity on human colon, prostate, and myelogenous leukemia cell lines, as well as murine melanoma cell lines. Although a significant increase in the number of apoptotic cells was observed, this action could not be associated with caspase-3 activation.…”

Section: Salazinic Acidmentioning

confidence: 99%

Bioactive Lichen Secondary Metabolites and Their Presence in Species from Chile

Poulsen-Silva,

Gordillo-Fuenzalida,

Atala

et al. 2023

Metabolites

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Lichens are symbiotic organisms composed of at least one fungal and one algal species. They are found in different environments around the world, even in the poles and deserts. Some species can withstand extreme abiotic conditions, including radiation and the vacuum of space. Their chemistry is mainly due to the fungal metabolism and the production of several secondary metabolites with biological activity, which have been isolated due to an increasing interest from the pharmaceutical community. However, beyond the experimental data, little is known about their mechanisms of action and the potential pharmaceutical use of these kinds of molecules, especially the ones isolated from lesser-known species and/or lesser-studied countries. The main objective of this review is to analyze the bibliographical data of the biological activity of secondary metabolites from lichens, identifying the possible mechanisms of action and lichen species from Chile. We carried out a bibliographic revision of different scientific articles in order to collect all necessary information on the biological activity of the metabolites of these lichen species. For this, validated databases were used. We found the most recent reports where in vitro and in vivo studies have demonstrated the biological properties of these metabolites. The biological activity, namely anticancer, antioxidant, and anti-inflammatory activity, of 26 secondary metabolites are described, as well as their reported molecular mechanisms. The most notable metabolites found in this review were usnic acid, atranorin, protolichesterinic acid, and lobaric acid. Usnic acid was the most investigated metabolite, in addition to undergoing toxicological and pharmacological studies, where a hepatotoxicity effect was reported due to uncoupling oxidative phosphorylation. Additionally, no major studies have been made to validate the pharmacological application of these metabolites, and few advancements have been made in their artificial growth in bioreactors. Despite the described biological activities, there is little support to consider these metabolites in pharmaceutical formulations or to evaluate them in clinical trials. Nevertheless, it is important to carry out further studies regarding their possible human health effects. These lichen secondary metabolites present a promising research opportunity to find new pharmaceutical molecules due to their bioactive properties.

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Antitumor effect of depsidones from lichens on tumor cell lines and experimental murine melanoma

Cited by 13 publications

References 32 publications

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties

Bioactive Lichen Secondary Metabolites and Their Presence in Species from Chile

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