Antileishmanial Activity of Aldonamides and<i>N</i>-Acyl-Diamine Derivatives

Coimbra, Elaine Soares; Almeida, Camila G. de; Júnior, Wilson Valente; Reis, Roberta C. N. Dos; Almeida, Ana C. F. De; Forezi, Luana da S. M.; Almeida, Mauro Vieira de; Hyaric, Mireille Le

doi:10.1100/tsw.2008.100

Cited by 8 publications

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References 18 publications

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“…Nevertheless, all therapies have some limitations as several toxic effects and unaffordable cost (5,6). In a previous study, we have shown that lipophilic diamine derivatives have proved inhibitory effects in Leishmania (7,8). So, the aim of this study was to evaluate in vitro some lipidic amino alcohols against different species of Leishmania .…”

Section: Values Of Ic50 (μM) For the Activity Of The Compounds Againmentioning

confidence: 99%

Synthesis and Antileishmanial Activity of Lipidic Amino Alcohols

et al. 2010

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In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC 50 below 10 lM. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms. Leishmaniasis is a complex infection caused by multiple species of the intracellular protozoan parasite Leishmania. This disease is endemic in some tropical areas of the world and affects an estimated 12 million people with 2 million new cases annually (1,2). The clinical spectrum of leishmaniasis is varied and encompasses subclinical (inapparent), localized (skin lesions) and disseminated infection (cutaneous, mucosal or visceral) (2). Visceral manifestation is the more severe form of leishmaniasis, because it is fatal if 4a n = 9; R1=R2=H; m=1 5a n = 11; R1=R2=H; m=1 5b n = 11; R1=H; R2=CH 3 ; m=1 5c n = 11; R1=2-hydroxyethyl; R2=H; m=1 5d n = 11; R1=R2=H; m=2 6a n = 13; R1=R2=H; m=1 6b n = 13; R1=H; R2=CH 3 ; m=1 6c n = 13; R1=2-hydroxyethyl; R2=H; m=1 6d n = 13; R1=R2=H; m=2 7a n = 15; R1=R2=H; m=1 H 3 C (CH 2 )n a b 11a n = 9; R1=H; R2=2-hydroxyethyl 11b n = 9; R1=H; R2=3-hydroxypropyl 11c n = 9; R1=R2=2-hydroxyethyl 11d n = 9; R1=H; R2=1,1-dimethyl-2-hydroxyethyl 12a n = 11; R1=H; R2=2-hydroxyethyl 12b n = 11; R1=H; R2=3-hydroxypropyl 12c n = 11; R1=R2=2-hydroxyethyl 12d n = 11; R1=H; R2=1,1-dimethyl-2-hydroxyethyl 2b n = 9 2c n = 11 2d n = 13 2e n = 15 9a n = 9 9b n = 11 8a n = 9 8b n = 11 1a n = 7 1b n = 9 1c n = 11 1d n = 13 1e n = 15 10a n =9 10b n =1111e n = 9; R1=H; R2=2-aminoethyl 11f n = 9; R1=H; R2=3-aminopropyl

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Section: Values Of Ic50 (μM) For the Activity Of The Compounds Againmentioning

confidence: 99%

Synthesis and Antileishmanial Activity of Lipidic Amino Alcohols

et al. 2010

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“…Additionally, due to the hydrophobic nature of imidazolidines, they were employed as ethylenediamine carriers. Recently, various derivatives of polyamines with antiparasitic activity have been introduced [9,10,11,12].…”

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confidence: 99%

Synthesis, Cytotoxicity, and Antileishmanial Activity of N,N'-Disubstituted Ethylenediamine and Imidazolidine Derivatives

Carvalho

Machado

Paula

et al. 2010

The Scientific World JOURNAL

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This paper describes the preparation of N,N'-disubstituted ethylenediamine and imidazolidine derivatives and their in vitro biological activities against Leishmania species. Of the nine synthesized compounds, five displayed a good activity in both L. amazonensis and L. major promastigotes. The compounds 1,2-Bis(p-methoxybenzyl)ethylenediamine (4) and 1,3-Bis(p-methoxybenzyl)imidazolidines (5) showed the best activity on intracellular amastigotes, with IC50 values of 2.0 and 9.4 μ/mL, respectively. In addition, none of compounds were cytotoxic against mammalian cells. The leishmanicidal activity can be related with inhibition of polyamine synthesis and cellular penetration within biological membranes.

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“…Otherwise, the chemotherapy against Chagas disease has been based mainly on nifurtimox and benznidazole, which is associated with limited efficacy, long‐term administration, and several side‐effects . In previous studies, we have shown that polyamine derivatives display inhibitory effects against several species of Leishmania , Trichomonas vaginalis , Trypanosoma cruzi , and Plasmodium berghei , providing evidence that lipophilic diamines can be considered important leading molecules for developing new antiparasitic drugs. Currently, we present the preparation and biological in vitro activity evaluation for one 1,2‐ethanediamine derivative, eight 1,4‐butanediamine derivatives, and eight 1,6‐hexanediamine derivatives against T. cruzi , L. braziliensis and L. chagasi to complement earlier results and contribute to the development of an attractive antiparasite molecule derived from constitutive polyamines.…”

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Assessment of Leishmanicidal and Trypanocidal Activities of Aliphatic Diamine Derivatives

et al. 2013

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Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was evaluated in vitro against Leishmania braziliensis, L. chagasi, and Trypanosoma cruzi. Twelve compounds presented anti-Leishmania and six showed anti-T. cruzi amastigote activity. Compound 14 (N-tetradecyl-1,4-butanediamine) was the most active against both L. braziliensis (IC50 = 2.6 μm) and L. chagasi (IC50 = 3.0 μm) which showed a selectivity index (SI) >100. N-decyl-1,6-hexanediamine (compound 9) presented an IC50 = 1.6 μm and SI >187 and was over six times more potent than the reference drug benznidazole against T. cruzi. Treatment of infected or uninfected macrophages with compounds 9 and 14 did not induce significant TNFα and NO production. Four compounds (15, 16, 22, and 23) inhibited 78.9%, 77.7%, 83.7%, and 70.1% of rTRLb activity, respectively, and compound 23 inhibited 73.3% of rTRTc activity at 100 μm. A concentration-dependent effect on mitochondrial membrane depolarization was observed in T. cruzi epimastigotes treated with compound 9, suggesting this mechanism may be involved in the trypanocidal effect. On the contrary, in L. braziliensis promastigotes treated with compound 14, no mitochondrial depolarization was observed. Our results demonstrate that N-decyl-1,6-hexanediamine and N-tetradecyl-1,4-butanediamine are promising molecules for the development of novel leading compounds against T. cruzi and Leishmania spp., particularly given a possible alternative mechanism of action.

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Antileishmanial Activity of Aldonamides andN-Acyl-Diamine Derivatives

Cited by 8 publications

References 18 publications

Synthesis and Antileishmanial Activity of Lipidic Amino Alcohols

Synthesis and Antileishmanial Activity of Lipidic Amino Alcohols

Synthesis, Cytotoxicity, and Antileishmanial Activity of N,N'-Disubstituted Ethylenediamine and Imidazolidine Derivatives

Assessment of Leishmanicidal and Trypanocidal Activities of Aliphatic Diamine Derivatives

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