Asperochramides A - D (1 - 4), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs (5 - 11), were isolated from the ethyl acetate extract of Aspergillus ochraceus. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction analysis. Compounds 3 and 4 represent a rare group of indole diketopiperazine alkaloid with a 3-hydroxyl-2-indolone moiety. The in vitro anti-inflammatory effects of compounds 1 and 3 - 11 were investigated by using LPS-stimulated murine macrophage RAW 264.7 cells. Compounds 1, 8, 10, and 11 showed potential anti-inflammatory activities.
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http://dx.doi.org/10.1002/cbdv.201700550 | DOI Listing |
Biochemistry
January 2025
Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
DtpC was isolated from the ditryptophenaline biosynthetic pathway found in filamentous fungi as a cytochrome P450 (P450) that catalyzes the dimerization of diketopiperazines. More recently, several similar P450s were discovered. While a vast majority of such P450s generate asymmetric diketopiperazine dimers, DtpC and other fungal P450s predominantly catalyze the formation of symmetric dimer products.
View Article and Find Full Text PDFBioorg Chem
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Beijing 100191, PR China. Electronic address:
Prenylated indole diketopiperazines represent a diverse array of alkaloids with complex chemical scaffolds and with a wide range of biological activities. Aiming to discover bioactive metabolites with structural novelty, genomic annotation in association with the MS/MS-based molecular networking demonstrated a deep-sea derived fungus Aspergillus puulaauensis F77 containing a profile of diketopiperazines. Targeted separation of the cultured fungus led to the isolation of 19 undescribed austamide-type diketopiperazines namely versicoines A-S.
View Article and Find Full Text PDFChem Biodivers
December 2024
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, P. R. China.
Three previously undescribed indole diketopiperazine alkaloids and seventeen known compounds were characterized by Aspergillus sp. JXC-5 by solid fermentation. Their structures were elucidated by spectroscopic methods and high-resolution electrospray ionization mass spectrometry, and the absolute configurations were further confirmed by electronic circular dichroism (ECD), induced CD spectra, and ML_J_DP4 methods.
View Article and Find Full Text PDFThe privileged fused-ring system comprising the bicyclo[2.2.2]diazaoctane (BDO) core is prevalent in diketopiperazine (DKP) natural products with potent and diverse biological activities, with some being explored as drug candidates.
View Article and Find Full Text PDFACS Chem Biol
November 2024
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich 8093, Switzerland.
ABCG2 is a multidrug transporter that protects tissues from xenobiotics, affects drug pharmacokinetics, and contributes to multidrug resistance of cancer cells. Here, we present tetracyclic fumitremorgin C analog Ko143 derivatives, evaluate their modulation of purified ABCG2, and report four high-resolution cryo-EM structures and computational analyses to elucidate their interactions with ABCG2. We found that Ko143 derivatives that are based on a ring-opened scaffold no longer inhibit ABCG2-mediated transport activity.
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