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Title: | Structure-based bioisosterism design, synthesis, biological evaluation and in silico studies of benzamide analogs as potential anthelmintics |
Authors: | Vairoletti, Franco Paulino, Margot Mahler, Graciela Salinas, Gustavo Saiz, Cecilia |
Type: | Artículo |
Descriptors: | BIOISOSTERISMO, NEMATODA, C. ELEGANS, ECHINOCOCCUS GRANULOSUS |
Issue Date: | 2022 |
Abstract: | A recent screen of 67,012 compounds identified a new family of compounds with excellent nematicidal activity: the ortho-substituted benzamide families Wact-11 and Wact-12. These compounds are active against Caenorhabditis elegans and parasitic nematodes by selectively inhibiting nematode complex II, and they display low toxicity in mammalian cells and vertebrate organisms. Although a big number of benzamides were tested against C. elegans in high-throughput screens, bioisosteres of the amide moiety were not represented in the chemical space examined. We thus identified an opportunity for the design, synthesis and evaluation of novel compounds, using bioisosteric replacements of the amide group present in benzamides. The compound Wact-11 was used as the
reference scaffold to prepare a set of bioisosteres to be evaluated against C. elegans. Eight types of amide replacement were selected, including ester, thioamide, selenoamide, sulfonamide, alkyl thio- and oxo-amides, urea and triazole. The results allowed us to perform a structure–activity relationship, highlighting the relevance of the amide group for nematicide activity. Experimental evidence was complemented with in silico structural studies over a C. elegans complex II model as a molecular target of benzamides. Importantly, compound Wact-11 was active against the flatworm Echinococcus granulosus, suggesting a previously unreported pan-anthelmintic potential for benzamides. |
Publisher: | MDPI |
IN: | Molecules v.27, n° 9, 2022.-- e2659 |
Citation: | Vairoletti, F, Paulino, M, Mahler, G, y otros. "Structure-based bioisosterism design, synthesis, biological evaluation and in silico studies of benzamide analogs as potential anthelmintics". Molecules. [en línea] 2022, vol. 27, n° 9, e2659. DOI: https://doi.org/10.3390/molecules27092659 |
License: | Licencia Creative Commons Atribución (CC - By 4.0) |
Appears in Collections: | Publicaciones académicas y científicas - Facultad de Química |
Files in This Item:
File | Description | Size | Format | ||
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AA Vairoletti, Francisco et al. Molecules v.27, 2022.-- e2659.pdf | 10,13 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License