دورية أكاديمية
Assessment of leishmanicidal and trypanocidal activities of aliphatic diamine derivatives.
| العنوان: | Assessment of leishmanicidal and trypanocidal activities of aliphatic diamine derivatives. |
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| المؤلفون: | Yamanaka CN; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Cx. postal 476, Florianópolis, SC, 88.040-970, Brazil., Giordani RB, Rezende CO Jr, Eger I, Kessler RL, Tonini ML, de Moraes MH, Araújo DP, Zuanazzi JA, de Almeida MV, Steindel M |
| المصدر: | Chemical biology & drug design [Chem Biol Drug Des] 2013 Dec; Vol. 82 (6), pp. 697-704. Date of Electronic Publication: 2013 Aug 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262549 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-0285 (Electronic) Linking ISSN: 17470277 NLM ISO Abbreviation: Chem Biol Drug Des Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford : Wiley-Blackwell, 2006- |
| مواضيع طبية MeSH: | Diamines/*pharmacology , Leishmania/*drug effects , Trypanocidal Agents/*pharmacology , Trypanosoma cruzi/*drug effects, Animals ; Bone Marrow Cells/cytology ; Cell Survival/drug effects ; Diamines/chemistry ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/parasitology ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/metabolism ; Trypanocidal Agents/chemistry ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | 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. (© 2013 John Wiley & Sons A/S.) |
| فهرسة مساهمة: | Keywords: Leishmania braziliensis; Leishmania chagasi; Trypanosoma cruzi; aliphatic diamines; leishmanicidal and trypanocidal activity |
| المشرفين على المادة: | 0 (Diamines) 0 (Trypanocidal Agents) 0 (Tumor Necrosis Factor-alpha) 31C4KY9ESH (Nitric Oxide) |
| تواريخ الأحداث: | Date Created: 20130720 Date Completed: 20140616 Latest Revision: 20131125 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/cbdd.12191 |
| PMID: | 23865595 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1747-0285 |
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| DOI: | 10.1111/cbdd.12191 |