New antitumour agents with α, β-unsaturated δ-lactone scaffold: Synthesis and antiproliferative activity of (−)-cleistenolide and analogues. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Benedeković, Goran; Kovačević, Ivana; Popsavin, Mirjana; Francuz, Jovana; Kojić, Vesna; Bogdanović, Gordana; Popsavin, Velimir
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3318
• Page End: 3321
• Publication Date: 2016-07-15
• Subjects: YRIOWDRUIKYFFH-LZLYRXPVSA-N -- QGKHSGKDKKNFHY-CSKARUKUSA-N -- LLQJCQPOMJOCDA-INMHGKMJSA-N -- XPQQBRXKTDIELM-UHFFFAOYSA-N; Cleistenolide -- Cleistenolide mimics -- Antitumour δ-lactones -- SAR -- Analogue synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.044
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A stereoselective total synthesis of (−)-cleistenolide (1 ) fromd -glucose has been achieved. This new approach for the synthesis of (−)-cleistenolide and analogues involves a one- C -atom degradation of the chiral precursor, ( Z )-selective Wittig olefination, followed by the final δ-lactonisation. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially 2, 4, 6-trichlorobenzoyl derivative12, which in the culture of MDA-MB 231 cells displayed the highest activity (IC50 0.02 μM) of all compounds under evaluation. A preliminary SAR study reveals the structural features that are beneficial for antiproliferative activity of synthesized δ-lactones, such as presence of either electron-withdrawing or electron-donating substituents in the aromatic ring, as well as the presence of cinnamoyl functionality instead of benzoyl group at the O-7 position.