Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kretschmer, N; Hufner, A; Durchschein, C; Popodi, K; Rinner, B; Lohberger, B; Bauer, R.
Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives.
Int J Mol Sci. 2021; 22(5):
Doi: 10.3390/ijms22052774
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- Führende Autor*innen der Med Uni Graz
- Kretschmer Nadine
- Co-Autor*innen der Med Uni Graz
- Lohberger Birgit
- Rinner Beate
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- Abstract:
- Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - chemical synthesis
- Antineoplastic Agents - chemistry
- Antineoplastic Agents - pharmacology
- Apoptosis - drug effects
- Cell Line, Tumor -
- Cyclopropanes - chemical synthesis
- Cyclopropanes - chemistry
- Cyclopropanes - pharmacology
- Humans -
- Melanoma - drug therapy
- Melanoma - metabolism
- Naphthoquinones - chemical synthesis
- Naphthoquinones - chemistry
- Naphthoquinones - pharmacology
- Find related publications in this database (Keywords)
- shikonin derivatives
- synthesis
- apoptosis
- cell cycle
- melanoma