Planta Med 2004; 70(6): 551-555
DOI: 10.1055/s-2004-827156
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Epimeric Withaphysalins from Leaves of Acnistus arborescens

Maria Leopoldina Veras1 , Maria Zeneide B. Bezerra1 , Raimundo Braz-Filho2 , Otilia Deusdênia L. Pessoa1 , Raquel Carvalho Montenegro3 , Cláudia do Ó Pessoa3 , Manoel Odorico de Moraes3 , Letícia Veras Costa-Lotufo3
  • 1Curso de Pós-Graduação em Química Orgânica, Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, Ceará, Brasil
  • 2Setor de Química de Produtos Naturais - LCQUI - CCT, Universidade Estadual do Norte Fluminense, Campos, Rio de Janeiro, Brasil
  • 3Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brasil
The authors are grateful to the Brazilian Agencies CAPES, CNPq, PRONEX, and FUNCAP for fellowship and financial support
Further Information

Publication History

Received: October 21, 2003

Accepted: March 1, 2004

Publication Date:
01 July 2004 (online)

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Abstract

Phytochemical analysis of the leaves of Acnistus arborescens (Solanaceae) resulted in the isolation of two new epimeric withaphysalins (17S,20R,22R)-5β,6β:18,20-diepoxy-4β,18-dihydroxy-1-oxowitha-24-enolide (2, 18R and 18S), together with the known withaphysalin F (1, 18R and 18S). Their structures were established by spectroscopic methods, including 2D NMR data and comparison with literature data. Compounds 1 and 2 displayed potent cytotoxic activities against several cancer cell lines with IC50 values in the range of 0.20 to 1.46 μg/mL for 1 and 0.89 to 8.08 μg/mL for 2. The strong cytotoxicity presented by 1 suggests that in this series of compounds, the 2,3-unsaturated ketone moiety is an important pharmacophoric unit. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2′-deoxyuridine incorporation after 24 hours of incubation on leukemic cells.

References

Dr. Letícia Veras Costa-Lotufo

Departamento de Fisiologia e Farmacologia

Faculdade de Medicina

Universidade Federal do Ceará

Rua Cel Nunes de Melo 1127

Caixa Postal-3157

60430-270 Fortaleza

Ceará

Brasil

Phone: +55-85-288-8255

Fax: +55-85-288-8333

Email: lvcosta@secrel.com.br