Cytotoxic effects of novel semisynthetic shikonin derivatives on melanoma cells

One of the most challenging problems in medicine is treatment of cancer, which is worldwide the second common cause of death. Malignant melanoma is an incurable type of cancer because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Enhancements in the understanding of melanoma biology, the identification and development of novel therapeutic strategies are still urgent research objectives. In the development of new anticancer drugs, natural products are of big relevance. About 87% of all newly approved anti-cancer drugs are natural products or derived from them [1]. Zicao, the roots of various members of the Boraginaceae family, have been used in TCM to treat macular eruption, measles and burns. Naphthoquinones, the main constituents of the roots, possess antitumor, wound healing, antiphlogistic and antibacterial activities [2]. In this study, the structure of shikonin was altered in order to obtain even more potent and specific derivatives. Previous investigations showed that the naphthoquinone moiety is more crucial for the entire activity than the side chain. There is evidence that the side chain can modify the total activity and can influence pharmacokinetics [3]. The cytotoxic potential of nine semisynthetic shikonin derivatives with modified side chain have been investigated by a XTT based viability assay in several melanoma cell lines (SbCl2, WM164, WM9 and MugMel2) at different concentrations. The identity and purity of the novel semisynthetic compounds has been checked by HPLC and NMR measurements. The most active compounds will be examined in more detail in future experiments.

[1] Newman et al, Journal Natural Products 2016, 79:629 – 661.

[2] Kretschmer et al, Journal Natural Products 2012, 75:856 – 869.

[3] Damianakos et al, Molecules 2012, 17:14310 – 14322.