Synthesis and biological evaluation of 2,3-diaryl isoquinolinone derivatives as anti-breast cancer agents targeting ERα and VEGFR-2.
The estrogen receptor α is recognized as important pharmaceutical target for breast cancer therapy, and vascular endothelial growth factor receptors (VEGFRs) play important roles in tumor angiogenesis including breast cancer. A series of 2,3-diaryl isoquinolinone derivatives were designed and synthesized targeting both estrogen receptor α (ERα) and VEGFR-2. Bioactivity evaluation showed that compounds 7c, 7d and 7f exhibited significant anti-proliferative and anti-angiogenesis activities via ERα and VEGFR-2 dependent mechanisms.
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Zhichao
Z
Tang
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Shaoxiong
S
Niu
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Fei
F
Liu
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Kejing
K
Lao
New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Jingshan
J
Miao
New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Jinzi
J
Ji
New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Xiang
X
Wang
New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Ming
M
Yan
New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Luyong
L
Zhang
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Qidong
Q
You
Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, PR China. Electronic address: xiaohong63xx@163.com.
Hong
H
Xiao
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: xianghua@cpu.edu.cn.
Hua
H
Xiang
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002645:Chickens; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D007546:Isoquinolines; D040301:Vascular Endothelial Growth Factor Receptor-2
2,3-Diaryl isoquinolinone derivatives; Anti-breast cancer; ERα; Synthesis; VEGFR-2