Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives
- Bioorg Med Chem Lett. 2021 Jun 1:41:127976. doi: 10.1016/j.bmcl.2021.127976.
- 1. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan, ROC.
- 2. School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, ROC.
- 3. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan, ROC; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC; Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, ROC. Electronic address: [email protected].
A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC50 = 1.39 µM). Some compounds were evaluated for DNA Topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed Topoisomerase inhibition activity with IC50 values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.