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

Abstract

Introduction: 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. Methods: 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. Results: O-methylarmepavine, a benzylisoquinolinic alkaloid, and a C 37 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 IC 50 of 23.3 µg/mL, and the acetogenins showed an IC 50 ranging from 25.9 to 37.6 µg/mL; in the amastigote assay, the IC 50 values ranged from 13.5 to 28.7 µg/mL. The cytotoxicity assay showed results ranging from 43.5 to 79.9 µg/mL. Conclusions: 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.

Phytochemical screening, cytotoxicity and acute toxicity of Annona vepretorum Mart (Annonaceae) leaf extracts

“…Thus, the methanol extract, crude hexane extract, partitioned hexane extract, chloroform and ethyl acetate presented promising results based on the IC 50 values, which could be attributed to the presence of alkaloids, flavonoids and terpenes, since these classes of secondary metabolites have cytotoxic activity [22][23][24].…”

Estudo químico e avaliação das atividades antiprotozoária e antimicobacteriana in vitro dos alcalóides isoquinolínicos e do óleo volátil de Annona crassiflora Mart. (Annonaceae)

“…Os fármacos deste grupo não são de uso convencional, podendo ser incluídos no tratamento, dependendo do histórico terapêutico do paciente, do potencial de resistência e dos custos, tendo em vista os efeitos colaterais (WHO, 2011, BRASIL, 2011, PEREZ-CAMACHO et al, 2011.…”

“…A terizidona (Figura 39) é um antibiótico de amplo espectro, selecionado para uso no Brasil, tendo em vista que apresenta boa tolerabilidade e baixa frequência de efeitos adversos em relação à cicloserina (BRASIL, 2011, VORA, 2010.…”

“…São mal toleradas, em decorrência de seus efeitos adversos, entre os quais estão: anorexia, náusea, vômitos, irritação gástrica, hipotensão postural, depressão, astenia, sonolência, distúrbios olfativos, diplopia, tontura, parestesias, dor de cabeça, nervosismo, tremores, erupções cutâneas alérgicas severas, estomatite, ginecomastia, impotência, menorragia, acne, alopecia e hepatite. Apesar de raros, houve relatos de convulsão e de neuropatia periférica (BRASIL, 2011, BRUNETON et al, 2011 (CHOLO et al, 2012, SEDDON et al, 2012, XU et al, 2011, SCHECTER et al, 2010, MIGLORI et al, 2009, RODLOFF et al, 2006, NUNN et al, 1993, WHITMAN & TUNKEL, 1992). , KISHORE et al, 2009, BAKKALI et al, 2008, TEMPONE et al, 2007, ANTHONY et al, 2001).…”

“…Considerando os alcalóides, particularmente, aqueles de núcleo isoquinolínico, mais exatamente, das classes aporfínica, oxoaporfínica, noraporfínica, tetrahidroprotoberberínica e aqueles de estrutura pirimidina-β-carbolínica, demonstraram importantes atividades anti-Leishmania e anti- (VILA-NOVA et al, 2011, FERNANDEZ et al, 2010, COSTA et al, 2006, QUEIROZ et al, 1996.…”