Synthesis and cytotoxicity evaluation of glycosidic derivatives of lawsone against breast cancer cell lines
- Bioorg Med Chem Lett. 2020 Jan 15;30(2):126817. doi: 10.1016/j.bmcl.2019.126817.
- 1. Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, 6627 Antônio Carlos, Belo Horizonte, MG 31.270-901, Brazil.
- 2. Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, 6627 Antônio Carlos, Belo Horizonte, MG 31.270-901, Brazil; Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, SC 88.040-970, Brazil. Electronic address: [email protected].
- 3. Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, 6627 Antônio Carlos, Belo Horizonte, MG 31.270-901, Brazil. Electronic address: [email protected].
Breast Cancer is the most incident and mortal Cancer type in women, with an estimated 2 million new cases expected by 2020 worldwide, with 600,000 deaths. As not all breast Cancer types respond to the anti-hormonal therapy, the development of new antineoplastic drugs is necessary. Lawsone (2-hydroxy-1,4-naphtoquinone) is a natural bioactive naphtoquinone displaying a range of activities, with dozens of derivatives described in the literature, including some glycosides possessing antitumor activity. Here, a series of glycosides of lawsone are reported for the first time and all compounds displayed good activity against the SKBR-3 cell line, with IC50 below 10 µM. The most promising derivative was the glycosyl triazole derived from peracetylated d-glucose (11), which showed better cytotoxicity against SKBR-3 (IC50 = 0.78 µM), being the most selective toward this tumoral cell (SI > 20). All compounds described in this work were more active than lawsone, indicating the importance of the carbohydrate and glycosyl triazole moiety for activity.