ISSN 2756-3375
African Journal of Immunology Research ISSN 2756-3375 Vol. 10 (5), pp. 001-015, May, 2024. Available online at www.internationalscholarsjournals.org © International Scholars Journals
Full Length Research Paper
Formulation of Basic Compounds as Arginase Inhibitors with Assessment Against Leishmania amazonensis
Núbia Boechat1*, Adriana S. Lages1, Osvaldo A. Santos-Filho1, Marcelo Genestra†2, Mônica M. Bastos1 and Warner B. Kover3
1Departamento de Pesquisa e Desenvolvimento de Fármacos, Instituto de Tecnologia em Fármacos (Farmanguinhos), FIOCRUZ, Rua Sizenando Nabuco, 100, Manguinhos, Rio de Janeiro - RJ, 21041-250, Brazil.
2Departamento de Imunologia, Instituto Oswaldo Cruz (IOC), Laboratório de Bioquímica de Tripanosomatídeos, FIOCRUZ, Av. Brasil, 4365, Manguinhos, Pavilhão Leônidas Deane, 4º andar, Rio de Janeiro - RJ, 21045-900, Brazil.
3Instituto de Química, Centro de Tecnologia, Universidade Federal do Rio de Janeiro, Bloco A, Lab A-613, Cidade Universitária, Rio de Janeiro - RJ, 21949-900, Brazil. †in memory
Accepted 11 March, 2024
Abstract
In this work, we synthesized substances and evaluated the potential leishmanicidal activity. Thirty-four (34) compounds from different chemical classes were selected for a simple synthesis in overall good yields, eight of which are not described in the literature. From the 34 compounds evaluated for preliminary leishmanicidal activity, three can be considered as prototypes for the development of leishmanicidal agents. Computational chemistry calculations, including comparative modeling of the enzyme arginase from Leishmania amazonensis and a molecular docking simulation of the synthesized molecules into the active site of the model were carried out.
Key words: Leishmaniasis, arginase, molecular docking, thiourea, bisguanidine, amidine, biological evaluation, comparative modeling.