title: Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.
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.
authors.affiliation: 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.
authors.forename: Hao-Meng
authors.initials: HM
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zhao-Liang
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Di
authors.initials: D
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Kui
authors.initials: K
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Zhen-Chuan
authors.initials: ZC
authors.lastname: Fan
authors.affiliation: Sphinx Scientific Laboratory, 1250 East State Street, Sycamore, IL 60178, USA.
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Yao
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005 Paris, France.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yu-Ou
authors.initials: YO
authors.lastname: Teng
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D002599:Chalcone
keywords: Antitumor agents; Apoptosis; Geranylated chalcones; K562 cell; Prenyled chalcones