Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity

Abstract

Endolichenic fungi (ELF) produce specialized metabolites that have various medicinal properties. Inhibition of tumor angiogenesis efficaciously suppresses many types of cancer. This study aimed to discover novel antiangiogenic agents from specialized metabolite extracts of ELF strains isolated from Korean lichens. The EtOAc extracts of 51 ELF strains were subjected to a screening pipeline consisting of cell viability, scratch wound healing, and Transwell migration assays. The EtOAc extract of Arthrinium sp. EL000127 showed the most potent inhibitory activity against the chemotactic migration of human umbilical vein endothelial cells (HUVEC). Targeted isolation on the major LC-MS peaks exhibited a previously known phthalide, 3-Omethylcyclopolic acid (1), and two unknown analogues of 1, 3-O-phenylethylcyclopolic acid (2) and 3-O-p-hydroxyphenylethylcyclopolic acid (3). The structures were characterized by MS and NMR analyses. All the isolates were acquired and applied to bioassays as racemates due to spontaneous racemization. Among the isolates, compound 3 effectively inhibits HUVEC motility by suppressing mRNA expressions of genes regulating epithelial cell survival and motility, which suggested that compound 3 is a potent antiangiogenic agent suitable for further exploration as a potential novel therapeutic against cancers.

Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction

“…A total of 5 × 10 4 CaCo2 and HCT116 cells in 100 μL DMEM containing 0.2% bovine serum albumin (BSA) were plated onto precoated inserts and incubated with UA or UA-linker or DMSO for 24 h. The lower chamber was filled with 600 μL of DMEM containing 0.2% BSA and 10 μg/mL fibronectin (EMD Millipore Corp., Billerica, MA, USA) as a chemoattractant. After incubation, cells in the upper chamber were fixed and stained using a Diff-Quick kit (Sysmex, Kobe, Japan) …”

“…After incubation, cells in the upper chamber were fixed and stained using a Diff-Quick kit (Sysmex, Kobe, Japan). 57 …”

A fatty acid-rich fraction of an endolichenic fungus Phoma sp. suppresses immune checkpoint markers via AhR/ARNT and ESR1

“…By using a rotary evaporator to evaporate EtOAc to dryness while maintaining a vacuum, 8.1 g of the crude extracts of EL006848 were obtained. For use in experiments, the crude extract was dissolved in 100% DMSO [ 31 ].…”

Endolichenic Fungi: A Promising Medicinal Microbial Resource to Discover Bioactive Natural Molecules—An Update

“…Moreover, 38 displayed significant inhibitory activity against Candida albicans, with an MIC value of 35 µg/mL. The daldipyrones A-C (41)(42)(43) were identified from an endolicanic fungus, Daldinia pyrenaica 047188, by Lee et al in 2023 [27]. Notably, the structures of daldipyrones A-C (41)(42)(43) were determined to share an unprecedented caged xanthone [6,6,6,6,6] polyketide future with a spiro-azaphilone unit using a spectroscopic analysis and chemical derivatization.…”

“…The daldipyrones A-C (41)(42)(43) were identified from an endolicanic fungus, Daldinia pyrenaica 047188, by Lee et al in 2023 [27]. Notably, the structures of daldipyrones A-C (41)(42)(43) were determined to share an unprecedented caged xanthone [6,6,6,6,6] polyketide future with a spiro-azaphilone unit using a spectroscopic analysis and chemical derivatization. Interestingly, the biological evaluation results illustrated that daldipyrenone A (41) displayed conspicuous antimelanogenic activity with an EC 50 value lower than that of the positive control as well as moderate adiponectin-secretion-promoting activity.…”