Planta Med 2008; 74 - PB131
DOI: 10.1055/s-0028-1084476

New cytotoxic withanolides from Withania aristata

GG Llanos 1, LB Araujo 2, IA Jiménez 1, L Moujir 2, IL Bazzocchi 1
  • 1Instituto Universitario de Bio-Orgánica „Antonio González“ and Instituto Canario de Investigación del Cáncer, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain
  • 2Departamento de Microbiología y Biología Celular, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38206 La Laguna, Tenerife, Spain

Cancer is one of the major human diseases and although considerable progress has been made in its treatment, the incidence and mortality rate still remain very high. Therefore, further research is needed for the development of new anticancer drugs. In this context, natural products are lead molecules for many of the drugs that are currently in clinical use, and in fact, over 60% of anticancer drugs available on the market are of natural origin [1].

The genus Withania (Solanaceae) is known for producing withanolides, which are steroidal lactone built on an ergostane skeleton of 28 carbons. Several of these substances have displayed various biological activities, such as anticancer, antiinflammatory and immunomodulatory activities [2].

In the search for new cytotoxic natural compounds, we have undertaken a systematic survey of the Canary Islands genera of Withania (Solanaceae) [3]. Therefore, the phytochemical analysis of the dichloromethane extract from the leaves of Withania aristata led to the isolation of eight withanolides, four of them not previously reported. Their structures were determined by means of spectroscopic studies, including 1D and 2D (COSY, ROESY, HSQC and HMBC) NMR experiments, and chemical correlations, whereas their absolute configurations were established by CD methods. Their cytotoxic activity against three cancer cell lines, HeLa (human carcinoma of the cervix), A-549 (human carcinoma of lung) and MCF-7 (human cancer breast) was evaluated by colorimetric method. Four of the compounds showed cytotoxicity at the log and lag phase of growth cycle (IC50<10µg/ml) against the cell lines used, and two of these exhibited potent activity against MCF-7 (IC50 0.6µg/ml), this effect being dependent on the time of exposure.

Acknowledgements: We are indebted to the DGES (CTQ2006–13376/BQU) and FICIC (01/2007) projects for financial support. G.G.LL. thanks to the Gobierno Autónomo de Canarias for a fellowship.

References: 1. Malik, F. et al. (2007) Life Sci. 80:1525–1538.

2. Veleiro, A. S.; Oberti, J. C.; Burton, G. (2005) Studies in Natural Products Chemistry (part L), Bioactive Natural Products. Atta-Ur-Raman Ed., Elsevier Science Publishers, Amsterdam. 32: 1019.

3. Martín-Herrera, D. et al. (2007)J. Ethnopharmacol. 113: 487–491.