Synthesis and anti-hepatocellular carcinoma activity of novel O-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.
10.1016/S1875-5364(18)30009-8
- Author:
Yu ZOU
1
;
Chang YAN
1
;
Jing-Chao LIU
1
;
Zhang-Jian HUANG
2
;
Jin-Yi XU
1
;
Jin-Pei ZHOU
1
;
Hui-Bin ZHANG
3
;
Yi-Hua ZHANG
4
Author Information
1. State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
2. State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpudahuang@163.com.
3. State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zhanghb80@163.com.
4. State Key Laboratory of National Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zyhtgd@163.com.
- Publication Type:Journal Article
- Keywords:
Anti-hepatocellular carcinoma activity;
Cytochrome P450;
NO release;
O(2)-Vinyl diazeniumdiolate;
Oleanolic acid
- MeSH:
Antineoplastic Agents;
chemical synthesis;
chemistry;
pharmacology;
Apoptosis;
drug effects;
Azo Compounds;
chemistry;
Carcinoma, Hepatocellular;
drug therapy;
pathology;
Cell Proliferation;
drug effects;
Cells, Cultured;
Drug Screening Assays, Antitumor;
Hep G2 Cells;
Hepatocytes;
drug effects;
metabolism;
pathology;
Humans;
Liver Neoplasms;
drug therapy;
pathology;
Nitric Oxide;
chemistry;
Nitric Oxide Donors;
chemical synthesis;
chemistry;
pharmacology;
Oleanolic Acid;
analogs & derivatives;
chemistry;
pharmacology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(12):928-937
- CountryChina
- Language:English
-
Abstract:
Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.
