Leishmanicidal Evaluation of Tetrahydroprotoberberine and Spirocyclic Erythrina-Alkaloids

Abstract

Leishmaniasis is one of the World's most problematic diseases in developing countries. Traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. In this work, two alkaloids 1 and 2 were obtained from Corydalis govaniana Wall and seven alkaloids 3-9, were obtained from Erythrina verna. The structures of the compounds were confirmed by mass spectrometry and 1D-and 2D-NMR spectroscopy. The leishmanicidal activity of compounds 1-9 against Leishmania amazonensis was tested on promastigote forms and cytotoxicity against J774 (macrophage cell line) was assessed in vitro. Compound 1 showed potent activity (IC 50 = 0.18 µg/mL), compared with OPEN ACCESSMolecules 2014, 19 5693 the standard amphotericin B (IC 50 = 0.20 µg/mL). The spirocyclic erythrina-alkaloids showed lower leishmanicidal activity than dibenzoquinolizine type alkaloids.

Gas‐phase dissociation study of erythrinian alkaloids by electrospray ionization mass spectrometry and computational methods

“…All the alkaloids employed in this study were obtained from E. verna as previously described in Callejon et al …”

The genus Erythrina L.: A review on its alkaloids, preclinical, and clinical studies

“…Callejon et al () isolated seven alkaloids from E. verna barks, which were tested against Leishmania amazonensis . Erythraline ( 40 ), 8‐oxo‐erythraline epoxide ( 44 ), crystamidine ( 45 ), and erythrinine ( 42 ) showed leishmanicidal activity with an IC 50 around 40–70 μg/ml, although these alkaloids also presented low selectivity index (CC 50 drug/IC 50 drug) when tested in macrophage cells (J774), indicating cytotoxicity for mammalian cells.…”

“…In addition, the study showed the effects of alcoholic extract against trypomastigote forms, reducing the number of parasites at 80% at 1,000 μg/ml. At the same concentration, the cytotoxic effects in macrophages for alcoholic extract of E. speciosa were not observed Callejon et al (2014). isolated seven alkaloids from E. verna barks, which were tested against Leishmania amazonensis.…”

Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

“…It is suggested that the GOV hydroxylation takes place at C (14), which tends to favor the formation of the m/z 324 by H 2 O loss with only a relatively small amount of m/z 194 by a RDA reaction. Considering the hydroxylation in different positions, like C(5) or C(6), both reactions (H 2 O loss and RDA) will not affect the occurrence of each one, or if it were in the positions C (8) or C (13), just one of the two reactions would be possible. Based on these data, M3 was tentatively proposed to be a mono-hydroxylated metabolite (Fig.…”

“…[7], a glabrous herb distributed in the Himalayas of Nepal, Pakistan and India [4,7]. GOV has been reported to show a different number of biological activities including anti-urease [7], leishmanicidal [8] and antinociceptive [4]. These activities have inspired the conduction of a study regarding its pharmacokinetic profile and in vitro metabolism.…”