Volatile Constituents of Endophytic Fungi Isolated from Aquilaria sinensis with Descriptions of Two New Species of Nemania.

Algae, bacteria, and fungi, as well as higher plants, produce a wide variety of secondary metabolites known as natural products. Natural products are well known as remarkable sources of many therapeutic agents. The genus Nemania is a wood-decaying fungus that belongs to family Xylariaceae. Nemania is often found as an endophyte in diverse hosts and some species are known to produce useful secondary metabolites. In this study, two Nemania species were isolated as an endophytic fungus from Aquilaria sinensis. Multi-gene phylogenetic studies showed that the newly described strains of Nemania are new to science, and this is the first report of Nemania from the host Aquilaria. One of the fermented species, Nemania aquilariae (KUMCC 20-0268), resulted in five sesquiterpenoids, which were previously reported from agarwood, and their structures were identified by gas chromatography-mass spectrometry (GC-MS). In addition, five different media were investigated in vitro to optimize conditions for growing the fungal biomass of Nemania aquilariae and N. yunnanensis.

Identification of Novel TRPC5 Inhibitors by Pharmacophore-Based and Structure-Based Approaches.

Canonical transient receptor potential-5 (TRPC5), which belongs to the subfamily of transient receptor potential (TRP) channels, is a non-selective cation channel mainly expressed in the central nervous system and shows more restricted expression in the periphery. TRPC5 plays a crucial role in human physiology and pathology, for instance, anxiety, depression, epilepsy, pain, memory and chronic kidney disease (CKD). However, due to lack of the effective and selective inhibitors, its physiological and pathological mechanism remains so far unknown. It is therefore pivotal to identify potential TRPC5 inhibitors. We have applied ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) methods. The pharmacophore models of TRPC5 antagonists generated by using the HypoGen and HipHop algorithms were used as a query model for the screening of potential inhibitors against the Specs database. The resultant hits from LBVS were further screened by SBVS. SBVS was carried out based on the homology model generation of human TRPC5, binding site identification, molecular dynamics optimization and molecular docking studies. In our systematic screening approaches, we have identified 7 hits compounds with comparable dock score after Lipinski and Veber rules, ADMET, PAINS analysis, cluster analysis, and similarity analysis. In conclusion, the current research provides novel backbones for the new-generation of TRPC5 inhibitors.