Antileishmanial and Trypanocidal Activities of Extracts and Aporphine Alkaloids Isolated from Monodora Genus (Annonaceae)

Abstract

Leishmaniasis and trypanosomiasis are protozoan diseases caused respectively by the kinetoplastid protozoan Leishmania parasites transmitted by the female phlebotomine sandflies and Trypanosoma parasites transmitted by the tsetse fly. In the search for agents from tropical medicinal plants to treat these two neglected tropical diseases, serially extracted petroleum ether, dichloromethane and methanol extracts of the leaves of Monodora crispata and Monodora brevipes, and eleven aporphines alkaloids isolated from the dried powdered leaves of the two plants were evaluated against Leishmania donovani promastigotes and Trypanosoma brucei brucei trypomastigotes. The extracts of both plants and the isolated compounds displayed varied levels of antiprotozoal activities. The oxoaporphine compounds, (+)-anolobine (7) and (+)-listeferine (8), exerted the most significant activity against L. donovani (IC 50 : 14.59 µM) and T. brucei brucei (LC 100 : 50.02 µM) respectively. This is the first report on the antiprotozoal activity of the isolated compounds. The results offer potential for further studies of the oxoaporphines for enhanced antiprotozoal activity.

Enantioselective synthesis and anti-parasitic properties of aporphine natural products

“…The aporphines comprise a large group of plant-derived tetracyclic alkaloids featuring a 1,2,3,4-tetrahydroisoquinoline motif. Many members of the aporphine family display interesting biological activities, such as anti-inflammatory [1], antimicrobial [2], anticancer [3,4] and antiparasitic [5,6] properties. In the latter context, a handful of aporphines have been evaluated for bioactivity against protozoan parasites; for example dicentrine, isolated from Cassytha filiformis L., demonstrated antiparasitic activity against Trypanosoma T. brucei, potentially by acting as an intercalating agent with the parasite DNA (the kinetoplast) [7].…”

A new natural indole and three aporphine alkaloids from Monodora bevipes Benth. (Annonaceae)

“…296.1281 mDa =0.1). The NMR spectra of 2 (Table 2) exhibited characteristic signals at δH 2.56 ppm (3H, s) and δC 42.7ppm, corresponding to an aporphine alkaloid, suchlike an N-methyl (Kablan et al, 2013;Dade et al, 2017). The combined analysis of its 13 C NMR and HSQC spectra revealed the presence of eighteen carbons: five methine, four methylene and eight quaternary carbon atoms.…”

“…1) were established according to their spectral data (NMR, IR and MS). Their stereochemistry was proposed on the basis of optical rotation measurement, in comparison with the literature (Hocquemiller et al, 1981;Spiff et al, 1984;Chang et al, 1995;Slvaki al., 1996;Kablan et al, 2013, Dade et al, 2017. [(1H, dd (8.4, 1.6), H-6)] and 8.18 (1H, H-4).…”

“…In addition to their medicinal potential, several species of Monodora are used to build housing. Monodora genus is a reach source of bioactive compounds like alkaloids (Leboeuf et al, 1982;Kablan et al, 2013, Dade et al, 2017, sesquiterpenes, monoterpenes, diterpenes (Etse et al, 1989), indole (Etse et al, 1989) and essential oils (Fournier et al, 1999;Owokotomo et al, 2012;Dje et al, 2016).…”

A recent update on new synthetic chiral compounds with antileishmanial activity

“…An enantioselective, modular, and convergent strategy for the synthesis of aporphines, another class of interesting natural alkaloids with interesting biological activities, [41][42][43][44][45][46] has been reported by Anderson et al as described in Scheme 5. 47 Phenylethylamines 31a,b are obtained from veratraldehyde and piperonal, through the respective β-nitrostyrenes.…”