In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis

Ramírez-Macías, Inmaculada; Marı́n, Clotilde; Chahboun, Rachid; Olmo, F.J.; Messouri, Ibtisam; Huertas, Óscar; Rosales, María J.; Gutiérrez-Sánchez, Ramón; Álvarez-Manzaneda, Enrique; Sánchez‐Moreno, Manuel

doi:10.1590/s0074-02762012000300012

Cited by 16 publications

(6 citation statements)

References 30 publications

(37 reference statements)

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“…On the other hand, semisynthetic ferruginol analogues 3 (Fig. 1) displayed antileishmanial activity (IC50= 22.3-35.0 µM) on intracellular amastigotes (L. infantum and L. braziliensis), being more active and less toxic than the reference drug glucantime [7]. Recently, Moreira et al reported on the antileishmanial activity of some dehydroabietic acid derivatives (e.g.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives

Dea-Ayuela

Bilbao-Ramos

Bolás‐Fernández

et al. 2016

European Journal of Medicinal Chemistry

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Abietane-type diterpenoids, either naturally occurring or synthetic, have shown a wide range of pharmacological actions, including antiprotozoal properties. In this study, we report on the antileishmanial evaluation of a series of (+)-dehydroabietylamine derivatives functionalized at C7 and/or C12. Thus, the activity in vitro against Leishmania infantum, Leishmania donovani, Leishmania amazonensis and Leishmania guyanensis, was studied. Most of the benzamide derivatives showed activities at low micromolar concentration against cultured promastigotes of Leishmania spp. (IC50 = 2.2-46.8 μM), without cytotoxicity on J774 macrophage cells. Compound 15, an acetamide, was found to be the most active leishmanicidal agent, though it presented some cytotoxicity on J774 cells. Among the benzamide derivatives, compounds 8 and 10, were also active against L. infantum intracellular amastigotes, being 18- and 23-fold more potent than the reference compound miltefosine, respectively. Some structure-activity relationships have been identified for the antileishmanial activity in these dehydroabietylamine derivatives.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives

Dea-Ayuela

Bilbao-Ramos

Bolás‐Fernández

et al. 2016

European Journal of Medicinal Chemistry

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“…1. The collection comprised the parent compound 1, its amide derivative 2, and compounds built from 1 using carbodiimide coupling and base hydrolysis 26,27 with L-amino acid derived side-chains, namely, compounds 3-19, and with D-amino acid side-chains (compounds [20][21][22][23][24][25][26][27][28][29][30][31]. Two additional compounds 17 and 29 were synthesized to complete the set, following the same procedures.…”

Section: Resultsmentioning

confidence: 99%

“…berries have also been reported to have antiprotozoal properties. [20][21][22][23][24] However, in some cases the testing was made only for extracellular parasitic forms whereas in others the compounds were either inactive or displayed limiting toxicity.…”

Section: Introductionmentioning

confidence: 99%

Antiprotozoal activity of dehydroabietic acid derivatives against Leishmania donovani and Trypanosoma cruzi

Vahermo¹,

Krogerus²,

Nasereddin

et al. 2016

Med. Chem. Commun.

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“…amazonensis intracellular amastigotes [ 44 ]. Ramirez-Macias et al [ 45 ], on the other hand, obtained the IC50 against intracellular amastigotes of Leishmania infantum chagasi at a 31.1 μM Glucantime concentration.…”

Section: Discussionmentioning

confidence: 99%

Immucillins Impair Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis Multiplication In Vitro

et al. 2015

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Chemotherapy against visceral leishmaniasis is associated with high toxicity and drug resistance. Leishmania parasites are purine auxotrophs that obtain their purines from exogenous sources. Nucleoside hydrolases release purines from nucleosides and are drug targets for anti-leishmanial drugs, absent in mammal cells. We investigated the substrate specificity of the Leishmania (L.) donovani recombinant nucleoside hydrolase NH36 and the inhibitory effect of the immucillins IA (ImmA), DIA (DADMe-ImmA), DIH (DADMe-ImmH), SMIH (SerMe-ImmH), IH (ImmH), DIG (DADMe-ImmG), SMIG (SerMe-ImmG) and SMIA (SerME-ImmA) on its enzymatic activity. The inhibitory effects of immucillins on the in vitro multiplication of L. (L.) infantum chagasi and L. (L.) amazonensis promastigotes were determined using 0.05–500 μM and, when needed, 0.01–50 nM of each drug. The inhibition on multiplication of L. (L.) infantum chagasi intracellular amastigotes in vitro was assayed using 0.5, 1, 5 and 10 μM of IA, IH and SMIH. The NH36 shows specificity for inosine, guanosine, adenosine, uridine and cytidine with preference for adenosine and inosine. IA, IH, DIH, DIG, SMIH and SMIG immucillins inhibited L. (L.) infantum chagasi and L. (L.) amazonensis promastigote growth in vitro at nanomolar to micromolar concentrations. Promastigote replication was also inhibited in a chemically defined medium without a nucleoside source. Addition of adenosine decreases the immucillin toxicity. IA and IH inhibited the NH36 enzymatic activity (Ki = 0.080 μM for IA and 0.019 μM for IH). IA, IH and SMIH at 10 μM concentration, reduced the in vitro amastigote replication inside mice macrophages by 95% with no apparent effect on macrophage viability. Transmission electron microscopy revealed global alterations and swelling of L. (L.) infantum chagasi promastigotes after treatment with IA and IH while SMIH treatment determined intense cytoplasm vacuolization, enlarged vesicles and altered kinetoplasts. Our results suggest that IA, IH and SMIH may provide new chemotherapy agents for leishmaniasis.

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In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis

Abstract: The activity of five (1)(2)(3)(4)(5)

Cited by 16 publications

References 30 publications

Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives

Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives

Antiprotozoal activity of dehydroabietic acid derivatives against Leishmania donovani and Trypanosoma cruzi

Immucillins Impair Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis Multiplication In Vitro

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