Planta Med 2008; 74 - PA151
DOI: 10.1055/s-0028-1084149

In vitro antiproliferative activity of Xanthones and Guttiferones from Securidaca spp

AL Meli 1, PC Castilho 2, JM Padrón 3
  • 1Department of Organic Chemistry, Faculty of Science, University of Yaounde I, PO Box 812, Yaounde, Cameroon
  • 2Centro de Quimica da Madeira, Dept. Quimica, Univ. Madeira, Campus Universitario da Penteada, 9000–390 Funchal, Portugal
  • 3BioLab, Instituto Canario de Investigación del Cáncer, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain

Twelve compounds xanthones, guttiferones and other benzophenones were isolated from plants used in African traditional medicine, including new and already known substances. The structure of each compound was determined by 1H- and 13C-NMR, FTIR, UV/Vis and HREIMS techniques. COSY, HMQC and HMBC experiments were used to determine homonuclear 1H, 1-bond 1H–13C and 2- and 2-bond 1H–13C connectivities, respectively.

The in vitro antiproliferative activity of this set of compounds was evaluated using the National Cancer Institute (NCI) protocol [1] after 48h of drug exposure using the sulforhodamine B (SRB) assay [2]. As a model for the anticancer activity we used the representative panel of human solid tumor cell lines A2780 (ovarian), SW1573 (non-small cell lung), WiDr (colon), HBL-100 (breast), HeLa (cervix) and T-47D (breast).

In addition to the antitumor activity, the lipophilicity (ClogP) of the compounds was evaluated by in silico calculation based on their chemical structure [3]. ClogP values were calculated to correlate lipophilicity with antitumor activity.

As a whole, lipophilicity is not sufficient to explain the observed differences in growth inhibition. However, the antiproliferative data reveal that the majority of the compounds are active against at least one cell line. The most antiproliferative compounds (FRGA1 and GSF1) showed GI50 values in the range 0.8–4.2µM, against all the cell lines. In terms of cytotoxicity, compound FRGA1 was the most potent with TGI and LC50 values ranging 4.3–7.7µM and 9.5–29µM, respectively.

References: 1. Skehan, P. et al. (1990)J. Natl. Cancer Inst. 82:1107

2. Miranda, P.O. et al. (2006) Chem Med Chem 1:323.

3. Software-predicted lipophilicity of the compounds was calculated with the program New ClogP accessible via Internet (–112/OLLM/111F98/newclogp.html)