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

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: 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. RESULTS: 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. 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.

Annona sp: Plants with multiple applications as alternative medicine - a review

Annona species have been used as a natural remedy for a variety of illnesses with antiparasitic, antispasmodic, antidiarrheal, antiulcer, sedative, analgesic, hypotensive, and vermifugal effects. These properties are due to the presence of a number of bioactive compounds on the leaves, fruit, seeds, and stem. The aim of this review is to show the main species of Annona, their medicinal properties and the chemical constituents that may be related to these effects. In the leaves it is possible to find acetogenins, annopentocins A, B, and C, cis- and trans-annomuricin-D-ones, goniothalamicin, arianacin, and javoricin, related to anticancer properties. Quercetin-3-O-glucoside, also found in the leaves mediates antidiabetic and antioxidative effects. In the fruit are found annonaine, nornuciferine and asimilobine, associated to antidepressive effects. In the seeds are found muricatetrocin A and muricatetrocin B, longifolicin, corossolin, corossolone, uvarigrandin A, bullatacin, squamotatin. These acetogenins are associated with anticancer effects. Cyclosquamosin B, quercetin, and cyclosquamosin from the seeds have respectively vasorelaxant, antithyroidal and, antiinflammatory activity. In the stem parts there are several components as N-trans-feruloyltyramine, N-p-coumaroyltyramine, and N-trans-caffeoyltyramine, lignans, syringaresinol, syringaldehyde, beta-sitosterol and beta-sitosterol-beta-D-glucoside which exhibit antiplatelet aggregation activity. Copaene, patchoulane, 1H-cycloprop (e) azulene and kaur-16-en-19-oic acid found in the barks exhibit significant central as well as peripheral analgesic and antiinflammatory activities. The properties of the biological compounds in Annona species support information that may provide validation for its medicinal uses, but further studies should be performed to establish ideal and safe doses of consumption to ensure the effectiveness of the benefits. © 2012 Bentham Science Publishers.