In vitro cytotoxic, antifungal, trypanocidal and leishmanicidal activities of acetogenins isolated from Annona cornifolia A. St. -Hil. (Annonaceae)

Abstract

Annona cornifolia A. St. -Hil. is a small annual perennial tree found in the Brazilian savannah; their green fruit is popularly used in the treatment of ulcers. The acetogenins isolated from the seeds of Annona cornifolia previously showed to possess antioxidant activity. In continuation of our investigations on the biological activities of acetogenins, four binary mixtures and ten pure adjacent bis-tetrahydrofuran annonaceous acetogenins were evaluated: the cytotoxic (against three human tumor cell lines), antifungal (against Paracoccidioides brasiliensis), trypanocidal (against Trypanosoma cruzi) and leishmanicidal (against Leishmania amazonensis) activities. Acetogenins presented cytotoxic activity confirming their potential use in anti-cancer therapy. Regarding leishmanicidal and trypanocidal activities, an inhibition of 87% of L. amazonensis amastigotes and 100% of T. cruzi amastigotes and trypomastigotes was observed, when tested at the concentration of 20 µg mL -1 . Moreover, six acetogenins showed more activity against all the three tested isolates of P. brasiliensis than trimethoprim-sulfamethoxazole, a drug used for treating paracoccidioidomycosis. Thus, acetogenins may be an alternative in treating a number of diseases that have a huge impact on millions of people worldwide. This paper reports for the first time the antifungal, leishmanicidal and trypanocidal activities for these acetogenins.

Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

“…The present study demonstrated the antifungal activity of liriodenine against three fungal strains of the genus Paracoccidioides ; however, greater activity was observed against yeasts of the genus Cryptococcus and against the thermally dimorphic fungus Histoplasma capsulatum . Among the studies focusing on the genus Paracoccidioides , two extracts derived from the genus Annona [ 46 , 47 ] and three evaluated compounds extracted from other plant species [ 48 - 50 ] were used. In this respect, Lima et al [ 46 ] evaluated the activity of fatty acid methyl esters (FAMEs) against 12 clinical isolates of P. brasiliensis by the broth microdilution method and observed inhibition of all isolates, with MIC values ranging from 3.4 to 55.5 μg.mL -1 .…”

“…This MIC range was similar to that observed in the present study. In another study, Lima et al [ 47 ] investigated the activity of acetogenins extracted from Annona cornifolia against Pb01 and Pb18 by the broth microdilution method. Concentrations of 1.17 to 150 μg.mL -1 were tested.…”

Traditional Uses, Phytochemistry and Pharmacological Activities of Annonacae

“…The cytotoxicity of annonacin has also been demonstrated against bladder cancer (T24), breast cancer (MCH7) and skin cancer (BCC-1) with IC 50 s 0.324, 0.433 and 0.427 µg/mL, respectively [ 172 ]. The cytotoxicity of five other acetogenins (squamocin M, annofolin, isolongimicin B, glaucanisin, and annotacin) isolated from A. cornifolia against human breast cancer (MCF-7) was reported, with IC 50 s of approximately 0.3 µM [ 173 ]. In an in vitro study, the annoaceous acetogenins laherradurin and cherimolin-2 isolated from A. diversifolia were shown to have ED 50 s of 0.015 and 0.05 µg/mL, respectively, against the cervical cancer cell line (HeLa) [ 174 ].…”

Antidiabetic activity of Annona crassiflora (Annonaceae)

“…Medicinal plants are defined as those capable of producing active ingredients that treat several diseases and hence achieving an important role in global health (Lima et al, 2014). Studies show that, in Brazil, about 91% of the population makes use of some medicinal plants, and 46% of them keep these plants homegrown (Ethur et al, 2011).…”