Nature‐Inspired Chemistry of Complex Alkaloids: Combining Targeted Molecular Networking Approach and Semisynthetic Strategy to Access Rare Communesins in a Marine‐Derived Penicillium expansum

• Published in: Chemistry : a European journal Vol. 29; no. 38; pp. e202300103 - n/a
• Main Authors: Hoang, Thi Phuong Thuy, Roullier, Catherine, Evanno, Laurent, Kerzaon, Isabelle, Gentil, Emmanuel, Robiou du Pont, Thibaut, Nazih, El‐Hassane, Pouchus, Yves François, Bertrand, Samuel, Poupon, Erwan, Grovel, Olivier
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 06-07-2023; Wiley-VCH Verlag
• Subjects: Alkaloids; Alkaloids - chemistry; Biological Products - metabolism; Biological Products - pharmacology; Chemical Sciences; Chemistry; communesins; Congeners; Cytotoxicity; Fungi; Humans; Life Sciences; marine-derived fungi; mass spectrometry; Medicinal Chemistry; Microbiology and Parasitology; Mycology; Natural products; Networking; Penicillium; Penicillium expansum; semisynthesis; Toxicity; Tumor cell lines; semisynthesis; Penicillium expansum; natural products; mass spectrometry; marine-derived fungi; communesins; communesins, marine-derived fungi, mass spectrometry, natural products, Penicillium expansum, semisynthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202300103

Communesins are rare alkaloids isolated from fungi of the genus Penicillium. In this work, the extract of a marine‐derived Penicillium expansum strain was studied using targeted molecular networking approach allowing to detect 65 communesins including 55 new ones. A fragmentation pattern for dimethylvinyl communesins was established and a script was implemented allowing to predict the structure and map all communesins in a global molecular network. A semisynthetic strategy was carried out to obtain some minor congeners from the two isolated communesins A and B. Nine communesins were then synthetised: two of them were already described as produced by the studied strain; four are new natural products which occurrence in the extracts was confirmed; three are new semi‐synthetic analogues never described so far. These communesins were evaluated for their cytotoxicity on two human cancer cell lines KB and MCF‐7 leading to a preliminary study of their structure‐activity relationships.
Rare heptacyclic alkaloids, namely communesins, could be specifically targeted on a molecular network and further obtained by semisynthesis. This work describes a comprehensive strategy to access unrevealed chemodiversity from fungi.