Format

Send to

Choose Destination
Eur J Med Chem. 2014 Sep 12;84:173-80. doi: 10.1016/j.ejmech.2014.07.003. Epub 2014 Jul 3.

Methylenedioxy flavonoids: assessment of cytotoxic and anti-cancer potential in human leukemia cells.

Author information

1
Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea; Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
2
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal; Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India.
3
Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea.
4
Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India.
5
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal.
6
Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea. Electronic address: marcdiederich@snu.ac.kr.

Abstract

A new series of chalcones, flavanones and flavones with methylenedioxy group at the 3',4' position in chalcone, 7,8 position in flavanones and flavones with mono-, di- and trimethoxy groups in the benzaldehyde ring have been assessed for their effect on proliferation, cytotoxic potential and apoptosis in human leukemia cells. Among the tested compounds, the chalcone series showed the best activity and chalcone 3 (mono methoxy group at the ortho position in A-ring) showed a significant effect on down-regulation of cancer cell proliferation and viability in three different leukemia cell lines (K562, Jurkat, U937). The executioner caspase cleavage analyses indicated that the cytotoxic effect mediated by chalcone 3 is due to induction of apoptotic cell death. Interestingly, the cytotoxic effect was cell type-specific and targeted preferentially cancer cells as peripheral blood mononuclear cells (PBMCs) from healthy donors were less affected by the treatment compared to K562, Jurkat and U937 leukemia cells. Altogether our results indicate a potential drug candidate with interesting differential toxicity obeying Lipinski's rule of five.

KEYWORDS:

Anti-inflammatory; Chalcones; Cytotoxic; Flavanones; Flavones; Leukemia

PMID:
25016375
DOI:
10.1016/j.ejmech.2014.07.003
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center