(S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A

In this study, the inhibitory activities against human monoamine oxidases (hMAOs) were evaluated using a library of 195 endogenous lichen fungi from Ukraine. Among them, the extract ELF68 of the endogenous fungus Rosellinia corticium from the lichen Pseudevernia furfuracea (L.) Zopf. exhibited the strongest inhibitory activity against hMAO-A. Using the activity-guided method, (S)-5-methylmellein (5MM) was isolated from the extract and had an IC50 value of 5.31 µM for hMAO-A with a lower potency for hMAO-B (IC50 = 9.15 µM). Compound 5MM also moderately inhibited acetylcholinesterase (IC50 = 27.07 µM) but very weakly inhibited butyrylcholinesterase and β-secretase. Compound 5MM had a Ki value of 2.45 μM and was a reversible competitive inhibitor of hMAO-A. A molecular docking study predicted that (S)-5MM showed higher binding affinity for hMAO-A (−6.8 kcal/mol) than hMAO-B (−6.4 kcal/mol). Its isomer, (R)-5MM, exhibited lower binding affinities for hMAO-A (−6.6 kcal/mol) and hMAO-B (−5.2 kcal/mol), compared to (S)-5MM. The S-form interacted with hMAO-A through hydrogen bonding with the Phe208 residue (distance: 1.972 Å), while the R-form interacted with the Asn181 residue (2.375 Å). The results of an in silico pharmacokinetic analysis indicated that 5MM did not violate Lipinski’s five rules and showed high gastrointestinal absorption and blood–brain barrier permeability. These results suggest that 5MM can be considered a candidate in the treatment of neuropsychiatric disorders, such as depression and cardiovascular disease.

Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus Diaporthe mahothocarpus

Using 126 endogenous lichen fungus (ELF) extracts, inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) were evaluated. Among them, extract ELF29 of the endogenous fungus Diaporthe mahothocarpus of the lichen Cladonia symphycarpia showed the highest inhibitory activity against hMAO-A. Compounds alternariol (AT), 5′-hydroxy-alternariol (HAT), and mycoepoxydiene (MED), isolated from the extract, had potent inhibitory activities against hMAO-A with IC50 values of 0.020, 0.31, and 8.68 µM, respectively. AT, HAT, and MED are reversible competitive inhibitors of hMAO-A with Ki values of 0.0075, 0.116, and 3.76 µM, respectively. The molecular docking studies suggested that AT, HAT, and MED had higher binding affinities for hMAO-A (−9.1, −6.9, and −5.6 kcal/mol, respectively) than for hMAO-B (−6.3, −5.2, and −3.7 kcal/mol, respectively). The relative tight binding might result from a hydrogen bond interaction of the three compounds with a Tyr444 residue in hMAO-A, whereas no hydrogen bond interaction was proposed in hMAO-B. In silico pharmacokinetics, the three compounds showed high gastrointestinal absorption without violating Lipinski’s five rules, but only MED showed high probability to cross the blood–brain barrier. These results suggest that AT, HAT, and MED are candidates for treating neuropsychiatric disorders, such as depression and cardiovascular disease.

Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus Daldinia fissa

Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as Daldinia fissa) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC50 = 3.23 µM) compared to MAO-A (IC50 = 13.97 µM). HMC is a reversible competitive inhibitor with a Ki value of 0.896 µM. No cytotoxicity was observed in normal and cancer cells at 50 µM of HMC. HMC showed blood–brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (−7.3 kcal/mol) was higher than that of MAO-A (−6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 Å), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.

Platythecium seychellense, a new species in the family Graphidaceae (lichenized Ascomycota: Ostropales) from the Seychelles and a world key to the genus

The new corticolous lichen fungus Platythecium seychellense is described from the Seychelles. Morphological characters as well as distribution and resemblance to related species are discussed. The species is characterized by a crustose, grey-green, smooth thallus lacking lichen substances, elongate and slender apothecia having flat, red-brown discs and grey 3-septate ascospores. A world key to all currently known species in the genus is presented.

Neosergipea, a new name for the lichen fungus Sergipea, with an updated phylogeny and notes on the genus Dichosporidium (lichenized Ascomycota: Arthoniales: Roccellaceae)

The new name Neosergipea M. Cáceres, Ertz & Aptroot is introduced to replace Sergipea M. Cáceres, Ertz & Aptroot, which is a later homonym of Sergipea Regali, Uesugui & Santos, a genus of fossil pollen. Using the small subunit of the mitochondrial rDNA cistron, we present an updated phylogeny of the Enterographa clade in Roccellaceae which includes the genera Dichosporidium, Enterographa, Erythrodecton, Mazosia, and Neosergipea. While in a previous analysis the relationship between Neosergipea and Dichosporidium was unresolved, our results suggest Neosergipea to be an unsupported sister to Dichosporidium s. lat. The latter potentially represents two distinct genera, differing in ascospore type.

Dictyonema coppinsii, a new name for the European species known as Dictyonemainterruptum (Basidiomycota: Agaricales: Hygrophoraceae), with a validation of its photobiont Rhizonema (Cyanoprokaryota: Nostocales: Rhizonemataceae)

The lichenized basidiomycete known as Dictyonemainterruptum is a widely distributed but rare, oceanic, western European species known from the British Isles, the Pyrenees, the Azores, and Madeira. Unfortunately, the name has never been validly published. The species was first described in the cyanobacterial genus Calothrix in 1833, which predates the starting point of heterocystous bacterial nomenclature, 1 January 1886. The epithet was never subsequently included in a validly published binomial and its combination into Dictyonema was therefore invalid as well. There was also controversy about whether the epithet applied to the cyanobacterial photobiont (as originally intended) or to the lichen fungus (as proposed later). Because of the lack of a valid description for this epithet, we have chosen to establish a new name, Dictyonema coppinsii Lücking, Barrie & Genney, for the lichenized fungus at hand, whereas the cyanobacterial photobiont is validated with the genus name Rhizonema Lücking & Barrie, adopting the epithet interruptum for it, and placed in a separate family, Rhizonemataceae Büdel & Kauff ex Lücking & Barrie.