A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.

Autor:	Ortiz-Pérez E; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Mendez-Alvarez D; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Juarez-Saldivar A; Unidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Reynosa 88710, México., Rodriguez-Moreno A; Laboratorio de Estudios Epidemiológicos, Clínicos, Diseños Experimentales e Investigación, Facultad de Ciencias Químicas, Universidad Autónoma 'Benito Juárez' de Oaxaca, México., De Alba-Alvarado M; Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, México., Gonzalez-Gonzalez A; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Vazquez K; Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Nuevo León, Gral. Escobedo 66050, México., Martinez-Vazquez AV; Laboratorio de Biotecnología Experimental, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Nogueda-Torres B; Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340., Lara-Ramírez EE; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Paz-Gonzalez AD; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México., Rivera G; Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México.
Jazyk:	angličtina
Zdroj:	Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2024 Jul 30. Date of Electronic Publication: 2024 Jul 30.
DOI:	10.2174/0115734064310458240719071823
Abstrakt:	Background: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. Objective: The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity. Method: A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2. Results: Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi. Conclusion: Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu