Trypanocidal activity of lipophilic diamines and amino alcohols

Júnior, Celso O. R.; Alves, Rosana; Rezende, Carlos A.; Costa, Cristiane França da; Silva, Heveline; Hyaric, Mireille Le; Fontes, Ana Paula Soares; Alves, Ricardo José; Romanha, Álvaro J.; Almeida, Mauro Vieira de

doi:10.1016/j.biopha.2010.06.002

Cited by 18 publications

(13 citation statements)

References 15 publications

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“…Because of the metabolic differences between healthy cells and tumor cells or between host cells and parasite cells, polyamine metabolism has been considered as a potential target for the chemotherapy of cancer and parasitosis [8]. Lipophilic diamines display inhibitory effects on Leishmania [9], Trichomonas vaginalis [10], and Trypanosoma cruzi [11]. These types of compounds can interact with membrane lipids and possibly, interfere with the lipid or the polyamine transport, or with the parasite metabolism [12].…”

Section: Introductionmentioning

confidence: 99%

Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: Synthesis, characterization, molecular modeling, and cytotoxic activity

Tavares

Teixeira

Lopes

et al. 2012

Journal of Inorganic Biochemistry

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Section: Introductionmentioning

confidence: 99%

Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: Synthesis, characterization, molecular modeling, and cytotoxic activity

Tavares

Teixeira

Lopes

et al. 2012

Journal of Inorganic Biochemistry

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“…The results showed that the tested compounds displayed higher activities against the T. cruzi culture form (IC 50 values ranging from 2.46-18.31 µM) (Table), being at least 10-fold more active compared to the previous data observed for the bloodstream form (Júnior et al 2010). A greater sensitivity of the amastigote form of T. cruzi has also been observed by other researchers using in vitro assays (da Silva et al 2010).…”

Section: Resultsmentioning

confidence: 79%

“…In a previous paper, we described the trypanocidal activity of lipophilic diamines and amino alcohols on bloodstream trypomastigotes, with all the tested compounds displaying an activity ranging from IC 50 values of 147 to 1,020 µΜ (Júnior et al 2010). In the present work, the activity of the same compounds was assayed using a tissue cell culture system, which is considered the in vitro method of choice for screening drugs for activity against T. cruzi (Canavaci et al 2010, Romanha et al 2010).…”

Section: Resultsmentioning

confidence: 99%

“…We have shown in previous studies that lipophilic diamine and amino alcohol derivatives display inhibitory effects against Leishmania (da Costa et al 2009), Trichomonas vaginalis (Giordani et al 2009), Mycobacterium tuberculosis (de Almeida et al 2007, Júnior et al 2009) and on bloodstream trypomastigote forms of T. cruzi (Júnior et al 2010). The aim of the present paper is a revaluation of the in vitro activity of these lipophilic diamines and amino alcohols in an assay consisting of L929 cells infected with both the amastigote and trypomastigote forms of the Tulahuen strain of T. cruzi .…”

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confidence: 99%

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The in vitro activity of fatty diamines and amino alcohols against mixed amastigote and trypomastigote Trypanosoma cruzi forms

Júnior

Hyaric

et al. 2014

Mem. Inst. Oswaldo Cruz

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Four diamines and three amino alcohols derived from 1-decanol, 1-dodecanol and 1,2-dodecanediol were evaluated in an in vitro assay against a mixture of trypomastigote and intracellular amastigote forms of Trypanosoma cruzi. Two of these compounds (6 and 7) showed better activity against both proliferative stages of T. cruzi than the positive control benznidazole, three were of similar potency (1, 2 and 5) and two were less active (3 and 4).

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“…(15,30) and Trypanosoma brucei brucei (31). Despite their potential antiprotozoal application, knowledge of their mechanisms of action on these organisms is limited and dispersed.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Action of Substituted β-Amino Alkanols on Leishmania donovani

Abengózar

Bustos

García-Hernández

et al. 2015

Antimicrob Agents Chemother

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Leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. Under this perspective, a quest for new chemical compounds is urgently needed. An N-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. Knowledge about its mechanism of action is still rather limited. In this work, we endeavored to define the leishmanicidal profile of such ␤-amino alkanol derivatives using a set of 15 N-mono-and disubstituted surrogates, tested on Leishmania donovani promastigotes and intracellular amastigotes. The best compound (compound 5), 2-ethylaminododecan-1-ol, had a 50% effective concentration (EC 50 ) of 0.3 M and a selectivity index of 72 for infected THP-1 cells and was selected for further elucidation of its leishmanicidal mechanism. It induced fast depletion of intracellular ATP content in promastigotes in the absence of vital dye intracellular entry, ruling out plasma membrane permeabilization as its origin. Confocal and transmission electron microscopy analyses showed that compound 5 induced severe mitochondrial swelling and vesiculation. Polarographic analysis using an oxygen electrode demonstrated that complex II of the respiratory chain (succinate reductase) was strongly inhibited by compound 5, identifying this complex as one of the primary targets. Furthermore, for other ␤-amino alkanols whose structures differed subtly from that of compound 5, plasma membrane permeabilization or interference with membrane traffic was also observed. In all, N-substituted ␤-amino alkanols were shown as appealing leishmanicidal candidates deserving further exploration.

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Trypanocidal activity of lipophilic diamines and amino alcohols

Cited by 18 publications

References 15 publications

Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: Synthesis, characterization, molecular modeling, and cytotoxic activity

Platinum(II) complexes containing long-chain hydrophobic N-alkyl-diamine ligands: Synthesis, characterization, molecular modeling, and cytotoxic activity

The in vitro activity of fatty diamines and amino alcohols against mixed amastigote and trypomastigote Trypanosoma cruzi forms

Mechanisms of Action of Substituted β-Amino Alkanols on Leishmania donovani

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