Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of -Kauranic Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Aug 7

PMID 34361708

Citations 1

Authors

Elena Pruteanu

Vladilena Girbu

Nicon Ungur

Leentje Persoons

Dirk Daelemans

Philippe Renaud

Veaceslav Kulcitki

Affiliations

Soon will be listed here.

Abstract

A convenient strategy for molecular editing of available -kauranic natural scaffolds has been developed based on radical mediated C-C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the -methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing -heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.

Citing Articles

Alkaloids in Future Drug Discovery.

Ferreira M Molecules. 2022; 27(4).

PMID: 35209135 PMC: 8875739. DOI: 10.3390/molecules27041347.

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