Novel NO-releasing plumbagin derivatives: Design, synthesis and evaluation of antiproliferative activity

Eur J Med Chem. 2017 Sep 8:137:88-95. doi: 10.1016/j.ejmech.2017.05.046.

Na Bao ¹, Jinfeng Ou ¹, Manyi Xu ¹, Fuqin Guan ², Wei Shi ¹, Jianbo Sun ³, Li Chen ⁴

Affiliations

1 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
2 Institute of Botany, Jiangsu Province, Chinese Academy of Science, Nanjing 210014, China.
3 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: sjbcpu@gmail.com.
4 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: chenli627@cpu.edu.cn.

PMID: 28558333 DOI: 10.1016/j.ejmech.2017.05.046

Abstract

A series of plumbagin/NO donor hybrids were designed, synthesized and evaluated in vitro against triple negative breast Cancer (MDA-MB-231), hepatocellular (HepG2) and lung (A549) carcinoma cells. Most furoxan-based plumbagin derivatives exhibited significantly superior potency compared to their parent compound. Noticeably, MDA-MB-231 cells are the most sensitive to these furoxan-based plumbagin derivatives as evidenced by IC₅₀ values ranging from 1.24 to 5.20 μM. Besides, NO released amounts detection of all hybrids suggested that in most cases, the antiproliferative activities were positively correlated with the levels of intracellular NO release in MDA-MB-231 cells. The most active compound (11a) also possessed higher chemical stability at different pHs (6.0, 7.4 and 8.0) than plumbagin. Together, the above promising results warrant the future potential of plumbagin/NO hybrids as the lead compounds against triple negative breast Cancer deserving further research.

Keywords

Cytotoxicity; NO-Releasing; Plumbagin; Selectivity; Stability.

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