Synthesis of novel anti-inflammatory usnic acid-based imidazolium salts

Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (−)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug—doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (−)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (−)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required.

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Synthesis and anti-inflammatory activity of novel triazole hybrids of (+)-usnic acid, the major dibenzofuran metabolite of the lichen Usnea longissima

Molecular Diversity ◽

10.1007/s11030-016-9716-5 ◽

2017 ◽

Vol 21 (2) ◽

pp. 273-282 ◽

Cited By ~ 10

Author(s):

Nagi Reddy Vanga ◽

Anudeep Kota ◽

Ramakrishna Sistla ◽

Mallavadhani Uppuluri

Keyword(s):

Usnic Acid ◽

Inflammatory Activity ◽

Usnea Longissima ◽

Anti Inflammatory

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

Pharmaceuticals ◽

10.3390/ph14121293 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1293

Author(s):

Elżbieta Studzińska-Sroka ◽

Aleksandra Majchrzak-Celińska ◽

Przemysław Zalewski ◽

Dominik Szwajgier ◽

Ewa Baranowska-Wójcik ◽

...

Keyword(s):

Usnic Acid ◽

Biological Properties ◽

Kynurenine Pathway ◽

Biologically Active ◽

Evernia Prunastri ◽

Biological Potential ◽

The Central Nervous System ◽

Anti Inflammatory ◽

Butyrylcholinesterase Activity ◽

Pharmacologically Active

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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In Silico Molecular Docking Studies of Lichen Metabolites against Cyclooxygenase-2 Enzyme

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v18i2.24304 ◽

2015 ◽

Vol 18 (2) ◽

pp. 90-96 ◽

Cited By ~ 4

Author(s):

Mohammad Firoz Khan ◽

Sabreena Aleem Nabila ◽

Ridwan Bin Rashid ◽

Mohammad Sharifur Rahman ◽

Abu Asad Chowdhury ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Usnic Acid ◽

Cyclooxygenase 2 ◽

Therapeutic Effects ◽

Lichen Metabolites ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

Cyclooxygenase-2 (COX-2) is an inducible enzyme that causes inflammation. COX-2 inhibitors are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicities. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular thrombotic events, including myocardial infarction. Therefore, there is still need to develop COX-2 inhibitors with better therapeutic effects and tolerability. The aim of the present study is to explore the anti-inflammatory activity of five lichen metabolites by conducting virtual screenings. In this regard, molecular docking simulations were carried out for the lichen metabolites namely atranorin, diffractic acid, lecanoric acid, salazinic acid and usnic acid with human COX-2 enzyme and the docked results were compared with the standard reference ligands (Celecoxib and Rofecoxib). Among all the docked ligands, the lecanoric acid demonstrated best binding affinity -9.83 kcal/mol followed by atranorin (-8.7 kcal/mol) and diffractic acid (-8.6 kcal/mol) which are comparable to the reference ligands celecoxib (-12.3 kcal/mol) and rofecoxib (-11.2 kcal/mol). The salazinic acid and usnic acid has shown binding affinity of -7.9 kcal/mol and -4.7 kcal/mol, respectively. Moreover, all the ligands except atranorin and diffractic acid satisfied Lipinskis rule of 5. From the docking results it was revealed that the lichen metabolites might have inhibitory activity against COX-2 enzyme, and are expected to be useful in conducting in vivo anti-inflammatory screenings on animal model which may lead to the development of more effective and potent new chemical entities with anti-inflammatory properties.Bangladesh Pharmaceutical Journal 18(2): 90-96, 2015

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Anti-inflammatory effects of usnic acid in an MPTP-induced mouse model of Parkinson’s disease

Brain Research ◽

10.1016/j.brainres.2019.146642 ◽

2020 ◽

Vol 1730 ◽

pp. 146642 ◽

Cited By ~ 1

Author(s):

Seulah Lee ◽

Yujeong Lee ◽

Sugyeong Ha ◽

Hae Young Chung ◽

Hangun Kim ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Usnic Acid ◽

Anti Inflammatory

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Poly-ε-Caprolactone Microsphere Polymers Containing Usnic Acid: Acute Toxicity and Anti-Inflammatory Activity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7392891 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Jéssica A. P. Barbosa ◽

Eryvelton S. Franco ◽

Camilla V. N. S. Silva ◽

Tatiane O. Bezerra ◽

Marllon A. N. Santana ◽

...

Keyword(s):

Particle Size ◽

Acute Toxicity ◽

Zeta Potential ◽

Encapsulation Efficiency ◽

Usnic Acid ◽

Polydispersity Index ◽

Inflammatory Activity ◽

Promising Alternative ◽

Anti Inflammatory ◽

Low Solubility

Usnic acid (UA) has been studied by its pharmacological properties; however, it presents moderate toxicity, low solubility, and absorption by biological membranes. The aim of this study was to develop poly-ε-caprolactone microsphere polymers containing UA (UA-micro) and evaluate their acute toxicity and anti-inflammatory activity. The microspheres were prepared by multiple emulsion technique (water/oil/water) and characterized by the encapsulation efficiency, particle size, polydispersity index, and zeta potential. The acute toxicity of UA and UA-micro (25–50 mg/kg; p.o.) was evaluated in mice. The anti-inflammatory activity of UA and UA-micro was evaluated by subcutaneous air pouch and carrageenan-induced paw edema in rat, with measurement of inflammatory cytokines and MPO levels. The UA presented encapsulation efficiency of 97.72%, particle size of 13.54 micrometers, polydispersity index of 2.36, and zeta potential of 44.5 ± 2.95 mV. The UA-micro presented lower acute toxicity (LD50 value up to 2000 mg/kg; p.o.) when compared to UA. UA-micro and UA (25 mg/kg) significantly reduced paw volume and decreased MPO levels, whereas only UA-micro (50 mg/kg) reduced significantly IL-1β, TNF-α, and NO levels in inflammatory exudate. These results suggest that controlled release systems, as microspheres, can be a promising alternative to reduce the toxicity of UA, making it a viable compound for inflammation therapy.

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