2. Academic Validation
  3. Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations

Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations

  • Eur J Med Chem. 2018 Jun 25:154:1-8. doi: 10.1016/j.ejmech.2018.04.047.
Na Bao 1,  Jinfeng Ou 1,  Na Li 1,  Pian Zou 1,  Jianbo Sun 2,  Li Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
  • 2 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. Electronic address: sjbcpu@gmail.com.
  • 3 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. Electronic address: chenli627@cpu.edu.cn.
PMID: 29772386 DOI: 10.1016/j.ejmech.2018.04.047
Abstract

High levels of both nitric oxide (NO) and Reactive Oxygen Species (ROS) could act as pro-apoptotic signals in cancerous cells. In this study, we conjugated diazeniumdiolates (NONOates), an important class of NO donors, with a natural occurring plumbagin (PL) which is primarily an excellent ROS inducer. Herein, a total of 12 novel plumbagin/NONOate hybrids have been synthesized and evaluated for their inhibitory effects on a panel of human Cancer cell lines (MDA-MB-231, A549, HepG2 and HCT-116 cells) and two normal human cells (HK-2 and WRL-68 cells). Among them, compounds 10a and 10b demonstrated superior potencies compared to their parent compound (IC50 values of 3.48-6.68 μM) against the above Cancer cell lines but weak inhibitory effects on normal cells. In concordance with their selective cytotoxicities, 10a and 10b released higher level of NO in Cancer cells than normal cells. Besides, the potent compound 10a induced Apoptosis of A549 cells in a concentration-dependent manner and resulted in more ROS generation compared with the parent compound plumbagin.

Keywords

Cytotoxicity; Nitric oxide; Plumbagin; Reactive oxygen species; Selectivity.

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