Volume 22, Issue 17, 1 September 2014, Pages 5013–5019
Navneet Kishorea,
- a Department of Plant Science, Plant Sciences Complex, University of Pretoria, Pretoria 0002, South Africa
- b Department of Natural Products, National Institute of Pharmaceutical Education and Research, Ahmedabad 380054, India
- c Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, Summerstrand Campus, Port Elizabeth 6031, South Africa
- d Pharmaceutical Sciences Division, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK
- Received 28 March 2014, Revised 29 May 2014, Accepted 6 June 2014, Available online 3 July 2014
Abstract
In
an effort to establish new candidates with enhanced anticancer activity
of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone)
previously isolated from the root extract of Euclea natalensis,
a series of 7-methyljuglone derivatives have been synthesized and
assessed for cytotoxicity on selected human cancer lines. These
compounds were screened in vitro for anticancer activity on MCF-7, HeLa,
SNO and DU145 human cancer cell lines by MTT assay. Most of them
exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8 μM followed by compound (5) with IC50
value of 10.1 and 9.3 μM, respectively. Structure–activity relationship
reveals that the fluoro substituents at position C-8 while hydroxyl
substituents at C-2 and C-5 positions played an important role in
toxicity.
Graphical abstract
Keywords
- Euclea natalensis;
- 7-Methyljuglone derivatives;
- Cytotoxicity;
- Cell cycle analysis;
- Cell apoptosis
Copyright © 2014 Elsevier Ltd. All rights reserved.
