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Planta Med 2017; 83(07): 661-671
DOI: 10.1055/s-0042-119864
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Synthetic Modification of 9α- and 9β-Hydroxyparthenolide by Heck or Acylation Reactions and Evaluation of Cytotoxic Activities

Abderrahman El Bouakher
1   Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II Casablanca, Mohammedia, Morocco
,
Badr Jismy
1   Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II Casablanca, Mohammedia, Morocco
,
Hassan Allouchi
3   Laboratoire de Chimie Physique, équipe RICM UMR-ISP 1282, Faculté de Pharmacie, Tours, France
,
Eric Duverger
4   GLYcoDIAG, Université dʼOrléans, Orléans, France
,
Latifa Barkaoui
1   Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II Casablanca, Mohammedia, Morocco
,
Ahmed El Hakmaoui
1   Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II Casablanca, Mohammedia, Morocco
,
Richard Daniellou
2   Institut de Chimie Organique et Analytique (ICOA), Université dʼOrléans, UMR CNRS 7311, Orléans, France
,
Gérald Guillaumet
2   Institut de Chimie Organique et Analytique (ICOA), Université dʼOrléans, UMR CNRS 7311, Orléans, France
,
Mohamed Akssira
1   Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II Casablanca, Mohammedia, Morocco
› Author Affiliations
Further Information

Publication History

received 13 April 2016
revised 12 October 2016

accepted 20 October 2016

Publication Date:
05 December 2016 (online)

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Abstract

Motivated by the widely reported anticancer activity of parthenolides and their derivatives, a series of new substituted parthenolides was efficiently synthesized. Structural modifications were performed at the C-9 and C-13 positions of 9α- and 9β-hydroxyparthenolide, which were isolated from the aerial parts of Anvillea radiata. Twenty-one derivatives were synthesized and evaluated for their in vitro cytotoxic activity against HS-683, SK-MEL-28, A549, and MCF-7 human cancer cell lines using the MTT colorimetric assay. Among the derivatives, seven exhibited excellent activity compared to 5-fluorouracil and etoposide against the four cell lines tested, with IC50 values ranging from 1.1 to 9.4 µM.

Key words

Anvillea radiate - Asteraceae - acylation - cytotoxic activity - Heck coupling - 9α-hydroxyparthenolide - 9β-hydroxyparthenolide

Supporting Information

1H and 13C NMR spectra of compound 3–23 are available as Supporting Information.

 

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