Leishmanicidal activity and cytotoxicity of compounds from two Annonacea species cultivated in Northeastern Brazil

Visceral leishmaniasis is endemic in 88 countries, with a total of 12 million people infected and 350 million at risk. In the search for new leishmanicidal agents, alkaloids and acetogenins isolated from leaves of Annona squamosa and seeds of Annona muricata were tested against promastigote and amas...

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Published in:	Revista da Sociedade Brasileira de Medicina Tropical Vol. 44; no. 5; pp. 567 - 571
Main Authors:	Vila-Nova, Nadja Soares, Morais, Selen Maiade, Falcão, Maria José Cajazeiras, Machado, Lyeghyna Karla Andrade, Beviláqua, Cláudia Maria Leal, Costa, Igor Rafael Sousa, Brasil, Nilce Viana Gramosa Pompeu de Sousa, Andrade Júnior, Heitor Francode
Format:	Journal Article
Language:	English
Published:	Brazil Sociedade Brasileira de Medicina Tropical 01-10-2011 Sociedade Brasileira de Medicina Tropical - SBMT Sociedade Brasileira de Medicina Tropical (SBMT)
Subjects:	4-Butyrolactone - analogs & derivatives 4-Butyrolactone - isolation & purification 4-Butyrolactone - pharmacology 4-Butyrolactone - toxicity Acetogenina Acetogenins - isolation & purification Acetogenins - pharmacology Acetogenins - toxicity Alcaloide benzilisoquinolinico Annona - chemistry Annona muricata Annona squamosa Benzylisoquinolines - isolation & purification Benzylisoquinolines - pharmacology Benzylisoquinolines - toxicity Chromatography, Gel Cytotoxicity Furans - isolation & purification Furans - pharmacology Furans - toxicity Introduced species Leaves Leishmania infantum - drug effects Leishmaniose Lethal Dose 50 Mutagenicity Tests Organic solvents Parasitic Sensitivity Tests Plant Extracts - isolation & purification Plant Extracts - pharmacology Plant Leaves - chemistry Seeds Seeds - chemistry Silica Solvents TROPICAL MEDICINE Trypanocidal Agents - isolation & purification Trypanocidal Agents - pharmacology Trypanocidal Agents - toxicity Vector-borne diseases Acetogenina Alcaloide benzilisoquinolinico Acetogenins Leishmaniose Leishmaniasis Benzylisoquinolinic alkaloids Annona squamosa Annona muricata
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Summary:	Visceral leishmaniasis is endemic in 88 countries, with a total of 12 million people infected and 350 million at risk. In the search for new leishmanicidal agents, alkaloids and acetogenins isolated from leaves of Annona squamosa and seeds of Annona muricata were tested against promastigote and amastigote forms of Leishmania chagasi. Methanol-water (80:20) extracts of A. squamosa leaves and A. muricata seeds were extracted with 10% phosphoric acid and organic solvents to obtain the alkaloid and acetogenin-rich extracts. These extracts were chromatographed on a silica gel column and eluted with a mixture of several solvents in crescent order of polarity. The compounds were identified by spectroscopic analysis. The isolated compounds were tested against Leishmania chagasi, which is responsible for American visceral leishmaniasis, using the MTT test assay. The cytotoxicity assay was evaluated for all isolated compounds, and for this assay, RAW 264.7 cells were used. O-methylarmepavine, a benzylisoquinolinic alkaloid, and a C37 trihydroxy adjacent bistetrahydrofuran acetogenin were isolated from A. squamosa, while two acetogenins, annonacinone and corossolone, were isolated from A. muricata. Against promastigotes, the alkaloid showed an IC50 of 23.3 µg/mL, and the acetogenins showed an IC50 ranging from 25.9 to 37.6 µg/mL; in the amastigote assay, the IC50 values ranged from 13.5 to 28.7 µg/mL. The cytotoxicity assay showed results ranging from 43.5 to 79.9 µg/mL. These results characterize A. squamosa and A. muricata as potential sources of leishmanicidal agents. Plants from Annonaceae are rich sources of natural compounds and an important tool in the search for new leishmanicidal therapies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0037-8682 1678-9849 1678-9849 0037-8682
DOI:	10.1590/S0037-86822011000500007