Leishmanicidal, Antifungal, and Cytotoxic Activity of Triterpenoid Glycosides Isolated from the Sea Cucumber Neothyone Gibbosa

Abstract

Neothyosides A -C, isolated from the body walls of the sea cucumber Neothyone gibbosa Deichmann, and a partially purified mixture of these saponins, were tested in vitro against promastigotes of two strains of Leishmania mexicana and a panel of several fungi using the broth microdilution technique. In addition, the cytotoxicity of these saponins was tested against Artemia salina. The IR, 1 H and 13 C NMR spectroscopic and FAB MS data of neothyoside C revealed that its structure was identical to that of pervicoside B, isolated from another sea cucumber species, Holothuria pervicax. Neothyoside C was the most active antiparasitic compound, inhibiting 100% of the promastigotes at 5 and 10 μg/mL of both L. mexicana strains. The mixture of saponins and pure neothyoside C showed the best activity against Aspergillus niger strains with MIC values between 15.6 μg/mL and 16.7 μg/mL for the mixture, and 4.65 μg/mL and 7.8 μg/mL for neothyoside C. Assays for cytotoxicity using Artemia salina showed that neothyosides A and C caused 50% brine-shrimp deaths at 130 and 63 μg/mL with this cytotoxicity 4 to 6 times greater than the concentration at which these compounds produce an antimicrobial effect. This is the first report describing the antileishmanial, antifungal, and cytotoxic activity of N. gibbosa saponins.

Marine natural products

“…732, 733 The known sea cucumber triterpene glycoside metabolites neothyosides A 734 and B 735 and pervicoside B 736 display leishmanicidal activity towards Leishmania mexicana as well as antifungal and cytotoxic properties. 737…”

A Visuomotor Model Enhances Human Position Sense

“…We excluded all trials with an error sound due to slow movement speed (on average 35 trials in Experiment 1 and 16 trials in Experiment 2). We also excluded trials with large deviations of movement endpoints from targets (>20° error in direction, or >6 cm error in extent), and movements whose trajectories were strongly curved (linearity index >2, defined as the maximum perpendicular distance of a movement trajectory to a straight line connection between home position and endpoint, divided by the distance between home position and endpoint; Atkeson & Hollerbach, 1985). Based on these criteria, on average four trials were excluded in Experiment 1, and six trials, on average, in Experiment 2.…”

Synthesis of Sea Cucumber Saponins with Antitumor Activities

“…The mixture was refluxed using an electric heating mantle and stirred for 10 min, cooled to rt, and then concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ EtOAc = 10:1) to afford 13 as a white solid (112 mg, 77% over three steps): [α] D 28 +23.9 (c 0.9, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ): δ 7.38−7.28 (m, 4H), 7.28−7.23 (m, 1H), 5.19 (dt, J = 5.3, 2.4 Hz, 1H), 4.72−4.61 (m, 3H), 4.44 (d, J = 11.9 Hz, 1H), 3.39 (s, 3H), 3.32 (dt, J = 7.5, 4.6 Hz, 1H), 3.05−2.98 (m, 1H), 2.91 (dd, J = 11.7, 4.0 Hz, 1H), 2.49−2.32 (m, 2H), 2.29 (dd, J = 10.4, 3.5 Hz, 1H), 1.39 (s, 3H), 1.18 (s, 3H), 0.99 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H), 0.86 (s, 3H); 13 3-O-Benzoyl-24-O-methoxymethyl-holostane-Δ 9(11) -12-ketone (14). To a mixture of crushed CrO 3 (172 mg, 1.72 mmol) in CH 2 Cl 2 (2 mL) was added 3,5-DMP (165 mg, 1.72 mmol) at −20 °C.…”

“…Pervicoside C ( 3 ) and its Δ 24(25) congener, namely, pervicoside B ( 2 ), were originally characterized in their desulfonated forms from sea cucumber Holothuria pervicax . Later on, they were isolated from other sea cucumber species, that is, Neothyone gibbosa, Holothuria fuscocinerea, Holothuria impatiens, and Actinopyga sp. , Pervicoside C ( 3 ) showed potent antitumor activities, with IC 50 values of 4.5 and 0.7 μM, respectively, against human leukemia HL-60 cells and human hepatoma BEL-7402 cells, that is similar to echinoside A ( 1 ). , To decipher the SAR and to find a practically useful synthetic lead compound of the sea cucumber saponins for further medicinal studies, we extended our efforts to the synthesis of pervicoside B ( 2 ) and C ( 3 ) and the structurally further simplified congeners.…”