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Antimicrobial Agents and Chemotherapy, July 2007, p. 2346-2350, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.01344-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Antiplasmodial Activity of Aryltetralone Lignans from Holostylis reniformis{triangledown}

Valter F. de Andrade-Neto,1,2,{dagger} Tito da Silva,3 Lucia M. Xavier Lopes,3* Virgílio E. do Rosário,4 Fernando de Pilla Varotti,1 and Antoniana U. Krettli1

Laboratório de Malaria, Centro de Pesquisas René Rachou/FIOCRUZ, 30190-002, Belo Horizonte, MG, Brazil,1 Departamento de Parasitologia, Universidade Federal de Minas Gerais, UFMG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil,2 Instituto de Química, Universidade Estadual Paulista, UNESP, C. P. 355, 14801-970, Araraquara, SP, Brazil,3 Instituto de Higiene e Medicina Tropical, Centro de Malaria e Doenças Tropicais, Universidade Nova de Lisboa, UNL, 1349-008, Lisboa, Portugal4

Received 26 October 2006/ Returned for modification 12 November 2006/ Accepted 3 April 2007

Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7'R,8S,8'S)-3',4'-methylenedioxy-4,5-dimethoxy-2,7'-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of ≤0.32 µM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

* Corresponding author. Mailing address: Instituto de Química, Universidade Estadual Paulista, UNESP, R. Francisco Degni s/n, C. P. 355, 14801-970, Araraquara, SP, Brazil. Phone: (55) 16-3301-6663. Fax: (55) 16-3301-6692. E-mail: lopesxl{at}iq.unesp.br

{triangledown} Published ahead of print on 16 April 2007.

{dagger} Present address: Departamento de Microbiologia e Parasitologia, Universidade Federal do Rio Grande do Norte, UFRN, 59072-970, Natal, RN, Brazil.

Antimicrobial Agents and Chemotherapy, July 2007, p. 2346-2350, Vol. 51, No. 7
0066-4804/07/$08.00+0     doi:10.1128/AAC.01344-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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