Synthesis of hydroxycinnamic acid derivatives as mitochondria-targeted antioxidants and cytotoxic agents.
10.1016/j.apsb.2016.05.002
- Author:
Jiyu LI
1
;
Dian HE
1
;
Baitao WANG
1
;
Ling ZHANG
1
;
Kun LI
1
;
Qinjian XIE
2
;
Lifang ZHENG
1
Author Information
1. School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
2. Gansu Corps Hospital of Chinese People Armed Police Forces, Lanzhou 730000, China.
- Publication Type:Journal Article
- Keywords:
Antiproliferative activities;
Hepatocellular carcinomas;
Hydroxycinnamic acids;
Mitochondrial dysfunction;
Mitochondrial permeability transition pore
- From:
Acta Pharmaceutica Sinica B
2017;7(1):106-115
- CountryChina
- Language:English
-
Abstract:
In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OHand ROOinduced lipid peroxidation. HOproduction was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines (HepG2, L02 and WI38) indicated that the MitoHCAs were selective for cancer cells. Interestingly, the MitoHCAs both with or without Catriggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochromerelease. In particular, an inhibitor of the mitochondrial permeability transition pore (mPTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs. Further studies focused on structural optimization of these compounds are onging.
