Journal
CHEMMEDCHEM
Volume 9, Issue 12, Pages 2725-2743Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201402292
Keywords
acylation; antitumor agents; aza compounds; cytotoxicity; goniothalamin
Categories
Funding
- Sao Paulo Research Foundation-FAPESP [2009/51602-5, 2012/18281-3, 2010/16990-1]
- CNPq
- Capes
Ask authors/readers for more resources
Herein we describe the synthesis of a focused library of compounds based on the structure of goniothalamin (1) and the evaluation of the potential antitumor activity of the compounds. N-Acylation of aza-goniothalamin (2) restored the in vitro antiproliferative activity of this family of compounds. 1-(E)-But-2-enoyl-6-styryl-5,6-dihydropyridin-2(1H)-one (18) displayed enhanced antiproliferative activity. Both goniothalamin (1) and derivative 18 led to reactive oxygen species generation in PC-3 cells, which was probably a signal for caspase-dependent apoptosis. Treatment with derivative 18 promoted AnnexinV/7-aminoactinomycinD double staining, which indicated apoptosis, and also led to G(2)/M cell-cycle arrest. In vivo studies in Ehrlich ascitic and solid tumor models confirmed the antitumor activity of goniothalamin (1), without signs of toxicity. However, derivative 18 exhibited an unexpectedly lower in vivo antitumor activity, despite the treatments being administered at the same site of inoculation. Contrary to its in vitro profile, aza-goniothalamin (2) inhibited Ehrlich tumor growth, both on the ascitic and solid forms. Our findings highlight the importance of in vivo studies in the search for new candidates for cancer treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available