In vitro anti-Leishmania activity and molecular docking of spiro-acridine compounds as potential multitarget agents against Leishmania infantum
| Autor: | Tatjana Souza Lima Keesen, Márcia Rosa de Oliveira, Rosane Nora Castro, Teresa Cristina Soares de Lima Grisi, Ian P.G. Amaral, Demetrius A. M. Araújo, Juliana da Câmara Rocha, Fernanda S. Almeida, Ricardo Olímpio de Moura, Frederico Fávaro Ribeiro, Michelangela Suelleny de Caldas Nobre, Gleyton Leonel Silva Sousa |
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| Rok vydání: | 2021 |
| Předmět: |
Erythrocytes
Clinical Biochemistry Protozoan Proteins Pharmaceutical Science Ligands Biochemistry Microbiology chemistry.chemical_compound Structure-Activity Relationship Parasitic Sensitivity Tests parasitic diseases Drug Discovery medicine Structure–activity relationship NADH NADPH Oxidoreductases Spiro Compounds Leishmania infantum Amastigote Molecular Biology biology Molecular Structure Chemistry Organic Chemistry Leishmaniasis medicine.disease Leishmania biology.organism_classification Trypanocidal Agents In vitro Molecular Docking Simulation DNA Topoisomerases Type I Infectious disease (medical specialty) Acridine Molecular Medicine Acridines Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 49 |
| ISSN: | 1464-3405 |
| Popis: | Leishmaniasis is an infectious disease with several limitations regarding treatment schemes. This work reports the anti-Leishmania activity of spiroacridine compounds against the promastigote (IC50 = 1.1 to 6.0 µg / mL) and amastigote forms of the best compounds (EC50 = 4.9 and 0.9 µg / mL) in Leishmania (L.) infantum and proposes an in-silico study with possible selective therapeutic targets for L. infantum. The substituted dimethyl-amine compound (AMTAC 11) showed the best leishmanicidal activity in vitro, and was found to interact with TryR and LdTopoI. comparisons with standard inhibitors were performed, and its main interactions were elucidated. Based on the biological assessment and the structure-activity relationship study, the spiroacridine compounds appear to be promising anti-leishmania chemotherapeutic agents to be explored. |
| Databáze: | OpenAIRE |
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