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Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12008/40994 How to cite
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

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