Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines

• Published in: Bioorganic & medicinal chemistry 2014-09, Vol.22 (17), p.5013-5019
• Main Authors: Kishore, Navneet, Binneman, Brigitte, Mahapatra, Anita, van de Venter, Maryna, du Plessis-Stoman, Debbie, Boukes, Gerhardt, Houghton, Peter, Marion Meyer, J.J., Lall, Namrita
• Format: Article
• Language: English
• Subjects: 7-Methyljuglone derivatives; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell apoptosis; Cell Cycle - drug effects; Cell cycle analysis; Cell Proliferation - drug effects; Cytotoxicity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Euclea natalensis; HeLa Cells; Humans; MCF-7 Cells; Molecular Structure; Naphthoquinones - chemical synthesis; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured; U937 Cells
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.06.013

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 6.8μM followed by compound (5) with IC50 value of 10.1 and 9.3μM, 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.