Toward “E‐Ring‐Free” Lamellarin Analogues: Synthesis and Preliminary Biological Evaluation

• Published in: Chembiochem : a European journal of chemical biology Vol. 24; no. 11; pp. e202300161 - n/a
• Main Authors: Rusanov, Daniil A., Mutasim Alfadul, Samah, Portnyagina, Ekaterina Yu, Silyanova, Eugenia A., Kuznetsov, Nikita A., Podpovetny, Kirill E., Samet, Alexander V., Semenov, Victor V., Babak, Maria V.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2023
• Subjects: [3+2]-cycloaddition; Alkaloids - chemistry; anticancer activity; Anticancer properties; Antineoplastic Agents - chemistry; Cell Line; Coumarins - chemistry; Cycloaddition; Cytotoxicity; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humans; Lamellar structure; lamellarin analogues; marine drugs; Neoplasms - drug therapy; pyridinium ylides; Structure-Activity Relationship; Toxicity; Tumor cell lines; lamellarin analogues; [3+2]-cycloaddition; anticancer activity; marine drugs; pyridinium ylides
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202300161

Since the discovery of anticancer properties of a naturally occurring hexacyclic marine alkaloid Lamellarin D, the attempts have been made to prepare its synthetic analogues and elucidate the effects of each structural component on their activity profile. While F‐ring‐free, A‐ring‐free and B‐ring‐open lamellarins are known, E‐ring‐free analogues have never been investigated. In this work, we developed a facile and straightforward synthetic method toward E‐ring‐free lamellarin analogues based on the [3+2]‐cycloaddition. For the first time, we prepared several pentacyclic lamellarin analogues without E‐ring in their structure and assessed their cytotoxicity in a panel of cancer cell lines in comparison with several hexacyclic lamellarins. E‐ring‐free lamellarins were devoid of cytotoxicity due to their poor solubility in cellular environment. For the first time, several pentacyclic E‐ring‐free lamellarin analogues were prepared using a new facile and straightforward synthetic method based on [3+2] cycloaddition. Their cytotoxicity was assessed in a panel of cancer cell lines in comparison with several hexacyclic lamellarins. E‐ring‐free lamellarins were devoid of cytotoxicity due to their poor solubility in cellular environment.