In vitro anti-Leishmania activity and molecular docking of spiro-acridine compounds as potential multitarget agents against Leishmania infantum

被引：18

作者：

Almeida, Fernanda S. ^{[1
,4
]}

Sousa, Gleyton L. S. ^{[3
]}

Rocha, Juliana C. ^{[4
]}

Ribeiro, Frederico F. ^{[5
]}

de Oliveira, Marcia Rosa ^{[6
]}

de Lima Grisi, Teresa Cristina Soares ^{[7
]}

Araujo, Demetrius A. M. ^{[2
]}

Nobre, Michelangela S. de C. ^{[8
]}

Castro, Rosane N. ^{[1
]}

Amaral, Ian P. G. ^{[2
]}

Keesen, Tatjana S. L. ^{[2
,4
]}

de Moura, Ricardo Olimpio ^{[9
]}

机构：

[1] Univ Fed Paraiba, Rede Nordeste Biotecnol, Programa Doutorado Biotecnol, BR-58051900 Joao Pessoa, Paraiba, Brazil

[2] Univ Fed Paraiba, Dept Biol Celular & Mol, BR-58059900 Joao Pessoa, Paraiba, Brazil

[3] Univ Fed Rural Rio de Janeiro, Programa Doutorado Quim, BR-23897000 Seropedica, RJ, Brazil

[4] Univ Fed Paraiba, Lab Imunol Doencas Infeciosas, BR-58051900 Joao Pessoa, Paraiba, Brazil

[5] Univ Fed Paraiba, Ctr Ciencias Exatas & Nat, BR-58059900 Joao Pessoa, Paraiba, Brazil

[6] Univ Fed Paraiba, Ctr Ciencias Exatas & Nat, Dept Biol Mol, BR-58059900 Joao Pessoa, Paraiba, Brazil

[7] Univ Fed Paraiba, Dept Biotecnol, BR-58051900 Joao Pessoa, Paraiba, Brazil

[8] Univ Fed Pernambuco, Programa Doutorado Ciencias Farmaceut, BR-50670901 Recife, PE, Brazil

[9] Univ Estadual Paraiba, Ctr Ciencias Biolag & Saude, BR-58429500 Campina Grande, Paraiba, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2021年 / 49卷

关键词：

Leishmaniasis; Antileishmanial activity; Acridine compounds; Multitarget agent; Structure-activity relationship; ANTILEISHMANIAL ACTIVITY; BIOLOGICAL EVALUATION; STEROL; 14-ALPHA-DEMETHYLASE; TRYPANOTHIONE REDUCTASE; QUINOLINE DERIVATIVES; DNA-TOPOISOMERASE; ACRIDINE/ACRIDONE; INHIBITION; PARAMETERS; BINDING;

D O I：

10.1016/j.bmcl.2021.128289

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu g/mL) and amastigote forms of the best compounds (EC50 = 4.9 and 0.9 mu g / 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 LdTopol. 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.

引用

页数：6

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