Document Type
Article
Publication Date
1-12-2026
Publication Title
ACS Omega
Disciplines
Biology | Chemistry | Parasitology
Abstract
Effective and safe treatments for neglected tropical diseases caused by parasites, such as Chagas disease and sleeping sickness, remain lacking, posing a significant challenge for researchers worldwide. The rational design of dimeric compounds inspired solely by the pharmacophoric core of benznidazole (2-nitroimidazole) has proven to be a promising strategy for antiparasitic development. Thus, in the present work, it was increased the linker between the active units (2-nitroimidazole) to improve the interaction with TcNTR, facilitating the bioactivation of the longest dimers. Biological assays confirmed this, demonstrating that all compounds were active against replicative intracellular amastigotes of Trypanosoma cruzi (Tulahuen C2C4-LacZ). Notably, longer-chain dimers exhibited remarkable potency (IC50 < 1.0 mu M). These compounds also showed significant activity against T. b. brucei and demonstrated very low cytotoxicity in mammalian cells, highlighting their selectivity, especially among the longer-chain dimers. These findings support the development of dimeric 2-nitroimidazole derivatives as selective agents against trypanosomes.
DOI
10.1021/acsomega.5c09284
Version
Publisher's PDF
Recommended Citation
Velez, Afonso Santine M.M.; Chaves, Otavio Augusto; Serpa, Carlos; Salem, Fatma M.; Li, Bibo Ph.D.; Su, Bin Ph.D.; Freire-de-Lima, Celio Geraldo; Decote-Ricardo, Debra; and Freire de Lima, Marco Edilson, "Contribution to the Chemotherapy of Human Trypanosomiasis: Design, Synthesis, and Biological Evaluation of Dimeric 2-Nitroimidazoles against Trypanosoma cruzi Amastigotes and Bloodstream Trypanosoma brucei" (2026). Biological, Geological, and Environmental Faculty Publications. 291.
https://engagedscholarship.csuohio.edu/scibges_facpub/291
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Volume
11
Issue
1
Comments
A.S.M.M.V. acknowledges CAPES for the PDSE fellowship (process 88881.933679/2024-01); O.A.C. acknowledges the Programa de Pos-Graduacao em Biologia Celular e Molecular at Oswaldo Cruz Foundation (Rio de Janeiro, Brazil) and CAPES for the grant PIPD (process SCBA 88887.082745/2024-00 with subproject 31010016). The Coimbra Chemistry Centre - Institute of Molecular Sciences (CQC-IMS) is supported by the Fundacao para a Ciencia e a Tecnologia (FCT), a Portuguese Agency for Scientific Research. CQC is funded by FCT through projects UID/PRR/00313/2025 (https://doi.org/10.54499/UID/PRR/00313/2025) and UID/00313/2025 (https://doi.org/10.54499/UID/00313/2025) and IMS through special complementary funds provided by FCT (project LA/P/0056/2020 https://doi.org/10.54499/LA/P/0056/2020)