Abstract
Several species of Aspidosperma plants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellow peroba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorum extracts, the plant activity against Plasmodium falciparum was evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium berghei in mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.
Highlights
Malaria, one of the most prevalent parasitic diseases in the world, still causes a high morbidity and is responsible for approximately 600,000 deaths yearly worldwide mainly due to Plasmodium falciparum (WHO 2014)
The 1H and 13C nuclear magnetic resonance (NMR) spectra showed downfield signals at δH 7.52 (1H, t, J= 7.5 Hz), 7.12 (1H, d, J = 7.5 Hz), 7.12 (1H, t, J = 7.5 Hz) and 7.48 (1H, d, J = 7.4 Hz), which correlate with the respective carbons at δC 117.9 (C-9), 121.6 (C-10), 119.5 (C-11) and 111.3 (C-12)
Additional signals were detected from four quaternary carbons, one with downfield signals at δC 175.4 (COOCH3) and the other four at δC 133.2 (C-2), 107.7 (C-7), 127.6 (C-8) and 137.7 C-20). 1H NMR spectrum showed the presence of an ethylidene side chain methyl group (C-19) at δH 1.67 (3H, d, J = 6.0 Hz) and an olefinic proton (C-18) at δH 5.64 (1H, q, J = 6.0 Hz) and at δH 4.30 (1H, sl) that correlated with δC 49.7
Summary
One of the most prevalent parasitic diseases in the world, still causes a high morbidity and is responsible for approximately 600,000 deaths yearly worldwide mainly due to Plasmodium falciparum (WHO 2014). This increasing global importance is a result of the spread of drug-resistant parasites, the current limitations of vector control and the absence of an effective vaccine. The activities of several plant species used against fever and malaria in Brazil have been tested against malaria parasites after fractionation and chemical characterisation (Krettli et al 2001, 2009, Frausin et al 2015). Drawing, displaying and characterising the chemical structures, substructures and reactions were performed using Marvin 5.4.1.1, 2011 (ChemAxon) (chemaxon.com)
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