Four new amide-containing diphenyl ethers, talaroacylamides A−D (1−4), and two new depsidones, talarodepsidones A−B (5−6), together with seven previously reported analogues 7−13 were isolated from the marine-derived fungus Talaromyces pinophilus ZS32. Their structures were elucidated by analysis of spectroscopic data, including NMR and HRESIMS, in combination with the modified Mosher’s method, NMR and ECD calculations and DP4+ probability analysis. Compounds 1−4 represent the first naturally occurring diphenyl ethers featuring an amide group at C-6 position. Compounds 1−3, 5, 6, 9, 11, and 13 exhibit weak antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Bacillusparanthracis and Bacillus subtilis. Compound 11 showed weak antifungal activity against Rhizoctonia solani, with an EC50 of 57.2 μg/mL. Further evaluation revealed increased membrane permeability, elevated markers of oxidative stress, mitochondrial membrane depolarization, decreased SDH activity in mycelial extracts, and reduced ATP content in R. solani exposed to compound 11.
Saringosterol (15), a phytosterol isolated as an epimeric mixture from the brown algae Sargassumringgoldianum and Lessonia nigrescens, is a potent antitubercular agent with a minimum inhibitory concentration (MIC) of 0.25 μg/mL and low cytotoxicity toward the Vero cell line. Likewise, several 5(6→7) abeo-sterols such as parguesterol A (18) are typically endowed with low cytotoxicity while displaying promising antitubercular activity with MICs ranging from 3.8 to 15 μg/mL. Based on these observations, we designed a chimeric sterol, hereafter known as leningosterol (30), which combines the most salient structural features of 15 and 18 believed to be responsible for antitubercular activity. Leningosterol (30) was synthesized in 10 steps from commercially available 3β-hydroxy-5-cholenic acid (32) with an overall yield of 7% and minimal utilization of protecting groups. When screened in vitro against Mycobacterium tuberculosis H37Rv, the MIC of 30 was unexpectedly higher than either 15 or 18. We also present a semi-synthesis of saringosterol (15) and reassess its purported potent antitubercular activity.
Two unprecedented triterpenoids, euphorusenes A (1) and B (2), together with fern-8-en-3β-ol (3), were isolated from Euphorbia humifusa. Compound 1 represented the first example of a triterpenoid possessing a 7/5/6/6/5 skeleton with migrated methyl-25, whereas 2 featured a distinct 7/5/6/6/5 cyclized scaffold characterized by methyl-25 migration, loss of C-4, C-23, and C-24, and a seven-membered lactone A ring. The structures of 1 and 2 were elucidated by spectroscopic methods and X-ray crystallographic analyses. Compound 1 displayed cytotoxicity against HCT-116 cells with an IC50 value of 8.0 ± 0.8 μM. Further biological evaluation revealed that 1 may trigger ferroptosis in HCT-116 cells by inhibiting GPX4.
Abstract Five new abyssomicin monomers (1−5), three new abyssomicin dimers (6−8), as well as the known abyssomicin analogues (9−13), were obtained from the endophytic Streptomyces sp. ns5-4 isolated from the medicinal herb Polygonatum sibiricum. The chemical structures of these compounds were identified by the analysis of the NMR, MS, and ECD spectra. The neuroprotective activities of the isolates were evaluated by the MTT assay. Abyssomicin 7 (3) and 9-O-methylabyssomicin 7 (4) showed significant neuroprotective activities against glutamate-induced excitotoxicity in HT22 cells, with EC50 values of 2.98 and 0.49 μM, respectively. Furthermore, compounds 3 and 4 exhibited negligible cytotoxicities toward normal HT22 cells at a concentration of 200 μM.
Abstract Feeding m-phenylenediamine to Myrothecium verrucaria HPU-ZMN produced eight new phenylpyrrole derivatives, myrodiamines A−H (1−8). Compounds 2 and 5 were likely purification artifacts. In contrast to the monofunctional aniline precursors used previously, the bifunctional diamine is processed along two routes: both amino groups engage in pyrrole formation to give dipyrrole dimers 1−5 or one is cyclized while the other is acylated, affording monopyrrole amides 6−8. Structures were elucidated by 1D/2D NMR and HRESIMS. Compound 3 showed potent cytotoxicity against K562 cells (IC50 = 0.073 μM) and promising activity against NCI-H446, NCI-H446/EP, and MDA-MB-231 cells (IC50 = 0.26−0.51 μM).
