Trypanocidal and leishmanicidal activity of six limonoids

Abstract

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1-4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5-46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis.

An In vitro and in silico investigation of the antitrypanosomal activities of the stem bark extracts of Anopyxis klaineana (Pierre) Engl

“…Plant terpenoids have been shown to have antitrypanosomal activities against Trypanosoma parasites [ 16 ]. Dihydro-7-Desacetyldeoxygedunin is structurally similar to two natural limonoids (7-deacetylgedunin and 7-deacetyl-7-oxogedunin) isolated from the roots of Pseudocedrela kotschyi, have been reported to have antitrypanosomal activities [ 86 ]. Helvolic acid which is an analog of Fusidic acid has been shown to possess antitrypanosomal activity against T. b. brucei parasite with IC 50 value of 5.08 μg/mL [ 87 ].…”

Pseudocedrela kotschyi : a review of ethnomedicinal uses, pharmacology and phytochemistry

“…Steverding et al. ( 2020 ) investigated the trypanocidal and leishmanicidal activities of six limonoids, namely, 9 , 10 , 13 , 14, 15 and 16 , against bloodstream forms of Trypanosoma bruce i and promastigotes of Leishmania major . All the six compounds showed anti-trypanosomal activity with IC 50 values ranging from 3.18 to 14.5 µM.…”

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

“…Compound 12 was also able to reduce the parasite load of infected macrophages with a 50% effective dose (ED 50 ) of 1.51 μM. At 10 μM, compound 12 completely killed intracellular amastigotes, in contrast to AmpB, which destroyed intracellular amastigotes at a concentration of 0.1 μM (Steverding et al., 2020). Both compound 12 and compound 13 have demonstrated antiparasitic activity, the former against P. falciparum (Sidjui et al., 2018) and the latter against T. brucei rhodesiense and L. donovani (Hay et al., 2007).…”