Fumarprotocetraric acid

Depsidones are some of the most abundant secondary metabolites produced by lichens. These compounds have aroused great pharmacological interest due to their activities as antioxidants, antimicrobial, and cytotoxic agents. Hence, this paper aims to provide up-to-date knowledge including an overview of the potential biological interest of lichen depsidones. So far, the most studied depsidones are fumarprotocetraric acid, lobaric acid, norstictic acid, physodic acid, salazinic acid, and stictic acid. Their pharmacological activities have been mainly investigated in in vitro studies and, to a lesser extent, in in vivo studies. No clinical trials have been performed yet. Depsidones are promising cytotoxic agents that act against different cell lines of animal and human origin. Moreover, these compounds have shown antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi, mainly Candida spp. Furthermore, depsidones have antioxidant properties as revealed in oxidative stress in vitro and in vivo models. Future research should be focused on further investigating the mechanism of action of depsidones and in evaluating new potential actions as well as other depsidones that have not been studied yet from a pharmacological perspective. Likewise, more in vivo studies are prerequisite, and clinical trials for the most promising depsidones are encouraged.

The aim of the present study is to provide a scientific rationale for the folklore usage of Cladonia pyxidata (L.) Hoffm. in treating tuberculosis (Tb). Through bioassay-guided isolation, antimycobacterial metabolites were isolated from under-investigated lichen C. pyxidata and examined against M.t H37Ra and six MDR strains. Further, the cytotoxicity of all isolated metabolites was evaluated on THP-1 macrophages. Bioassay-guided isolation of acetone extract of C. pyxidata yielded four metabolites, namely usnic acid, atranorin, barbatic acid, and fumarprotocetraric acid. Among those, the MIC values of usnic acid and fumarprotocetraric acid showed more effective in inhibiting the growth of six MDR strains, compared to first-line drug rifampicin. In addition, the 50% inhibitory concentration values of these two compounds on THP-1 were found to be far higher than MIC values against tested Tb strains, indicating that THP-1 macrophages were not harmfully affected at concentrations that were effective against M.t and MDR strains. The results exposed the traditional use of C. pyxidata for treating Tb, and the key metabolites were found to be usnic acid and fumarprotocetraric acid. The current study lends the first evidence for the presence of antimycobacterial compounds in C. pyxidata. Supplementary information: The online version contains supplementary material available at 10.1007/s13205-022-03159-6.

Background: Lichens are a composite consortium of a fungus and an alga. The symbiotic organisms are naturally equipped with distinct characteristics as compared to constituting organisms separately. Lichens, due to their peculiar anatomy and physiology, are the reservoir of more than 600 unique secondary metabolites, also known as 'lichen substances'. Since ancient times, many ethnic groups from various parts of the world have known about the applications of lichens as major provenance of food/fodder, medicine, dyes, spices, perfumes, etc. Lichen substances have shown impressive antioxidant, antimicrobial, antiviral, anti-tumor, and antiinflammatory activities under experimental conditions. Usnic acid, a well-known metabolite found in several species of lichens, possesses potent antioxidant and anti-inflammatory activities. It also has significant antiproliferative potential, as revealed through testing in different cancer cell lines. Atranorin, Lecanoric acid, Norstictic acid, Lobaric acid, Stictic acid, Ramalin, Gyrophoric acid, Salazinic acid, Protolichesterinic, and Fumarprotocetraric acid are some of the other purified lichen-metabolites with potent anti-cancer activities. Objective: This study presents an overview of lichen-derived extracts and compounds showing anti-cancer (or related) properties. Method: The review comprehends different studies (in vivo and in vitro) backing up the possibility of lichenextracts and metabolites towards their use as antioxidant, anti-proliferative, anti-inflammatory, and Epithelialmesenchymal transition (EMT) -inhibiting agents. Results: Various studies carried out to date show that lichen-extracts and metabolites have a range of anti-cancer and related properties that include anti-oxidative, anti-inflammatory, anti-proliferative, pro-apoptotic, and the potential of inhibition of cancer-associated EMT that is responsible for drug resistance and metastasis of cancer cells in a substantial proportion of cases. Conclusion: Lichens are the repertoire of a plethora of lichen-metabolites with significant anti-cancer potential. However, some of the critical 'anti-cancer related' properties, such as the ability of EMT-inhibition and the potential of induction of apoptosis, are relatively less studied for several lichen compounds. Additionally, many lichen compounds need to be purified at a larger scale to explore their anti-cancer potential.