Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs

Eur J Med Chem. 2015 Mar 6:92:439-48. doi: 10.1016/j.ejmech.2015.01.007.

Hao-Meng Wang ¹, Li Zhang ¹, Jiang Liu ¹, Zhao-Liang Yang ¹, Hong-Ye Zhao ¹, Yao Yang ¹, Di Shen ¹, Kui Lu ¹, Zhen-Chuan Fan ², Qing-Wei Yao ³, Yong-Min Zhang ⁴, Yu-Ou Teng ⁵, Yu Peng ⁶

Affiliations

1 Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China.
2 Key Laboratory of Food Nutrition and Safety (Tianjin University of Science & Technology), Ministry of Education, Tianjin 300457, PR China; Obesita & Algaegen LLC, College Station, TX 77845, USA.
3 Sphinx Scientific Laboratory, 1250 East State Street, Sycamore, IL 60178, USA.
4 Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005 Paris, France.
5 Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: tyo201485@tust.edu.cn.
6 Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: yupeng@tust.edu.cn.

PMID: 25590864 DOI: 10.1016/j.ejmech.2015.01.007

Abstract

Four natural Chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The Anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the Chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing Apoptosis.

Keywords

Antitumor agents; Apoptosis; Geranylated chalcones; K562 cell; Prenyled chalcones.

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