Fiche publication
Date publication
octobre 2022
Journal
Bioorganic & medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Pr LIRUSSI Frédéric
Tous les auteurs :
Qi X, Jiang S, Hui Z, Gao Y, Ye Y, Lirussi F, Garrido C, Xu L, He X, Bai R, Ye XY, Xie T
Lien Pubmed
Résumé
β-Elemene is the major constituent of the antitumor drugs elemene extract approved in China. By incorporating macrocyclization strategy into the β-elemene skeleton, we designed a series of novel macrocycles retaining three key carbon-carbon double bonds. Four different methods have been successfully developed for these challenging ring systems. A total of twenty-eight 14- to 24-membered macrocycles were synthesized. Most of these macrocycles exhibited good antitumor activity against several cancer cell lines (PC-3, A549, U87MG, U251 and HCT116), with up to 40 folds improvement of activity comparing to β-elemene. Additionally, X-ray single crystal structures of compounds Ic, Ip, and IIh were successfully solved as the proof of macrocycle formation. The results warrant the further investigation of this novel class macrocycles in pharmacokinetic and pharmacodynamics studies, which will be reported in due course.
Mots clés
Anti-proliferative activity, Antitumor, Macrocyclization, X-ray single crystal structure, β-elemene
Référence
Bioorg Med Chem. 2022 10 7;74:117049
