Heterodimeric diketopiperazine alkaloids from Penicillium expansum MA147 and their cytotoxicity.

Four previously undescribed heterodimeric diketopiperazine alkaloids, expansines A-D, were identified from the solid rice medium fermented by Penicillium expansum MA147, along with one new resorcylic acid derivative and five known compounds. Their structures and relative/absolute configurations were elucidated by interpretation of their spectroscopic data, quantum chemical calculations, and chemical conversion. Some obtained compounds were evaluated for the cytotoxicity against a triple-negative breast cancer cell line MDA-MB-231, and expansine C showed an IC50 value of 3.23 µM. In further mechanistic studies, we found that it might act by increasing the expression of ATP-binding cassette transporter A1 and reducing cellular cholesterol levels, suggesting its potential as a novel anti-cancer agent.

A Very Deep Graph Convolutional Network for 13C NMR Chemical Shift Calculations with Density Functional Theory Level Performance for Structure Assignment.

Nuclear magnetic resonance (NMR) chemical shift calculations are powerful tools for structure elucidation and have been extensively employed in both natural product and synthetic chemistry. However, density functional theory (DFT) NMR chemical shift calculations are usually time-consuming, while fast data-driven methods often lack reliability, making it challenging to apply them to computationally intensive tasks with a high requirement on quality. Herein, we have constructed a 54-layer-deep graph convolutional network for 13C NMR chemical shift calculations, which achieved high accuracy with low time-cost and performed competitively with DFT NMR chemical shift calculations on structure assignment benchmarks. Our model utilizes a semiempirical method, GFN2-xTB, and is compatible with a broad variety of organic systems, including those composed of hundreds of atoms or elements ranging from H to Rn. We used this model to resolve the controversial J/K ring junction problem of maitotoxin, which is the largest whole molecule assigned by NMR calculations to date. This model has been developed into user-friendly software, providing a useful tool for routine rapid structure validation and assignation as well as a new approach to elucidate the large structures that were previously unsuitable for NMR calculations.