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anti-inflammatory and antimicrobial responses. A,\u03b1-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. Methods: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of \u03b1,\u03b1-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. Results: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. Conclusions: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.<\/jats:p>","DOI":"10.3390\/ph16060782","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T02:58:48Z","timestamp":1684983528000},"page":"782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antiplasmodial, Trypanocidal, and Genotoxicity In Vitro Assessment of New Hybrid \u03b1,\u03b1-Difluorophenylacetamide-statin Derivatives"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-4441","authenticated-orcid":false,"given":"Carlos Fernando","family":"Araujo-Lima","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, LBC Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21041-250, RJ, 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Loureiro","family":"Rosario","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese de F\u00e1rmacos, Instituto de Tecnologia em F\u00e1rmacos, Farmanguinhos\u2014FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora Inacio","family":"Leite","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese de F\u00e1rmacos, Instituto de Tecnologia em F\u00e1rmacos, Farmanguinhos\u2014FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, ICB-UFRJ, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Caroline Campos","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Mal\u00e1ria, Centro de Pesquisas Ren\u00e9 Rachou, CPqRR\u2014FIOCRUZ, Belo 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