Abstract
This study describes the design, synthesis and trypanocidal evaluation of new azaheterocyclic derivatives (4-8). These compounds were designed as megazol (1) analogs based on bioisosterism tools and were synthesized to investigate the possible pharmacophoric contribution of the 1,2,4-triazole nucleus, the position of the heterocyclic nucleus and presence of the nitro group, to the activity against the bloodstream trypomastigote forms of Trypanosoma cruzi. The most potent compound was 6, a nitro derivative obtained by substitution of a thiadiazole by a triazole ring and by moving the nitro group from C-5 position, as in 1, to the C-4 position. Finally, we have used semi-empirical theoretical calculations to discuss the correlation of some stereo electronic properties with biological activity in an attempt to understand the possible mechanism of action of the designed series of compounds.
Keywords: Azaheterocyclic derivatives, megazol, Trypanosoma cruzi, Chagas disease, chemotherapy
Medicinal Chemistry
Title: Design, Synthesis and Activity Against Trypanosoma cruzi of Azaheterocyclic Analogs of Megazol
Volume: 3 Issue: 5
Author(s): A. S. Carvalho, R. F.S. Menna-Barreto, N. C. Romeiro, S. L. de Castro and N. Boechat
Affiliation:
Keywords: Azaheterocyclic derivatives, megazol, Trypanosoma cruzi, Chagas disease, chemotherapy
Abstract: This study describes the design, synthesis and trypanocidal evaluation of new azaheterocyclic derivatives (4-8). These compounds were designed as megazol (1) analogs based on bioisosterism tools and were synthesized to investigate the possible pharmacophoric contribution of the 1,2,4-triazole nucleus, the position of the heterocyclic nucleus and presence of the nitro group, to the activity against the bloodstream trypomastigote forms of Trypanosoma cruzi. The most potent compound was 6, a nitro derivative obtained by substitution of a thiadiazole by a triazole ring and by moving the nitro group from C-5 position, as in 1, to the C-4 position. Finally, we have used semi-empirical theoretical calculations to discuss the correlation of some stereo electronic properties with biological activity in an attempt to understand the possible mechanism of action of the designed series of compounds.
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Cite this article as:
Carvalho S. A., Menna-Barreto F.S. R., Romeiro C. N., de Castro L. S. and Boechat N., Design, Synthesis and Activity Against Trypanosoma cruzi of Azaheterocyclic Analogs of Megazol, Medicinal Chemistry 2007; 3 (5) . https://dx.doi.org/10.2174/157340607781745519
DOI https://dx.doi.org/10.2174/157340607781745519 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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