[11]-Chaetoglobosins from Pseudeurotium bakeri Induce G2/M Cell Cycle Arrest and Apoptosis in Human Cancer Cells

Abstract

Twelve new [11]-chaetoglobosins, chaetopseudeurins A–L (1–12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5–7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 μM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

“…In addition, Duan et al isolated 12 active alkaloids [11]-chaetoglobosin (1-12) from the endophytic fungus Pseudeurotium bakeri P1-1-1. By further analysis, [11]-chaetoglobosin B was found to have strong cytotoxic activity against MCF-7 cells and could activate apoptotic cell death via upregulating the expression of Bax, Cyt-C, and caspase-3 and downregulating the expression of Bcl-2 [93]. Yao et al found that chaetominine, a secondary metabolite isolated from Aspergillus fumigatus, has the competence to reverse drug resistance [94].…”

Indole-Containing Natural Products 2019–2022: Isolations, Reappraisals, Syntheses, and Biological Activities

“…Compounds 217 to 228 are novel [ 11 ]-chaetoglobosins isolated from Pseudeurotium bakeri , obtained from macrocoma moss (family: Orthotrichaceae). The alkaloids, containing an 11-membered macrocyclic ring, represent a rare motif as only seven naturally occurring [ 11 ]-chaetoglobosins have been reported [ 63 ]. Compound 229 is a novel indole-linked 2,5-diketomorpholine alkaloid with an unprecedented 6/5/6/6/5 core, while compound 230 contains an indole fused with pyrrole and possesses a 6/5/5 core [ 64 ].…”

“…Results revealed that reducing Δ19 caused a decrease in cytotoxicity ( 218 vs. 219 and 223 vs. 220 ), which infers that structural rigidity is required to exhibit cytotoxicity. Interestingly, the geometric conformation of Δ19 did not significantly influence activity, as evident when comparing the activities of the Z-isomer (271) and the E-isomer ( 272 ) [ 63 ]. No cytotoxicity or antibacterial activity was detected when compounds 229 and 230 were tested.…”