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  • Title: Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives.
    Author: He YF, Nan ML, Sun JM, Meng ZJ, Li W, Zhang M.
    Journal: Bioorg Med Chem Lett; 2013 May 01; 23(9):2543-7. PubMed ID: 23558236.
    Abstract:
    In the present investigation, 16 new rotundic acid (RA) derivatives modified at the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 <10 μM. The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis. The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase-3 and Bax, and decreasing protein expression of Bcl-2. In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate.
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