<i>N</i>-(4-Methoxyphenyl)Pentanamide, a Simplified Derivative of Albendazole, Displays Anthelmintic Properties against the Nematode <i>Toxocara canis</i>

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art_SILVA_iNi4MethoxyphenylPentanamide_a_Simplified_Derivative_of_Albendazole_Displays_Anthelmintic_2022.PDF (720.62 KB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER SOC MICROBIOLOGY
Autores
SILVA, Tais C.
MENGARDA, Ana C.
LEMES, Bruna L.
SOUZA, Dalete Christine S.
LAGO, Joao Henrique G.
MORAESA, Josue de
Citação
MICROBIOLOGY SPECTRUM, v.10, n.4, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. In this study, a simplified compound, N-(4-methoxyphenyl)pentanamide (N4MP), based on the structure of the most widely used anthelmintic (albendazole), was chemically prepared using 4-anisidine and pentanoic acid. N-(4-Methoxyphenyl)pentanamide was evaluated in vitro against the nematode Toxocara canis, an ascarid roundworm of animals that can infect humans. Similar to albendazole, bioassays showed that N-(4-methoxyphenyl)pentanamide affected the viability of parasites in a time- and concentration-dependent manner. Interestingly, N-(4-methoxyphenyl)pentanamide showed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Pharmacokinetic, drug-likeness, and medicinal chemistry friendliness studies demonstrated an excellent drug-likeness profile for N-(4-methoxyphenyl)pentanamide as well as an adherence to major pharmaceutical companies' filters. Collectively, the results of this study demonstrate that the molecular simplification of albendazole to give N-(4-methoxyphenyl)pentanamide may be an important pipeline in the discovery of novel anthelmintic agents. IMPORTANCE Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. Considering this scenario, the present study reports the preparation of N-(4-methoxyphenyl)pentanamide (N4MP), a simplified molecule based on the structure of the most widely used anthelmintic (albendazole). N4MP was evaluated in vitro against the nematode Toxocara canis, a common ascarid roundworm of domestic animals that can infect humans. Similar to albendazole, bioassays showed that N4MP affected the viability of parasites in a time- and concentration-dependent manner but displayed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Therefore, this study demonstrates that the molecular simplification of albendazole to give N4MP may be an important pipeline in the discovery of novel anthelmintic agents.
Palavras-chave
neglected diseases, antiparasitic agents, molecular simplification, albendazole, Toxocara canis, toxocariasis, helminthiasis
URI
https://observatorio.fm.usp.br/handle/OPI/56100
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - LIM/06