Antileishmanial Activity, Toxicity and Mechanism of Action of Complexes of Sodium Usnate with Lanthanide Ions: Eu(III), Sm(III), Gd(III), Nd(III), La(III) and Tb(III)

被引：3

作者：

da Silva, Fernanda ^{[1
]}

Rizk, Yasmin Silva ^{[1
]}

das Neves, Amarith Rodrigues ^{[1
]}

Lourenco, Estela Mariana Guimaraes ^{[2
]}

Ferreira, Alda Maria Teixeira ^{[3
]}

Monteiro, Melquisedeque Mateus ^{[4
]}

de Lima, Denis Pires ^{[2
]}

Perdomo, Renata Trentin ^{[4
]}

Bonfa, Iluska Senna ^{[5
]}

Toffoli-Kadri, Monica Cristina ^{[5
]}

Duarte, Adriana Pereira ^{[6
]}

Nunes, Daniel Mendes ^{[7
]}

Martines, Marco Antonio Utrera ^{[6
]}

Piranda, Eliane Mattos ^{[1
]}

de Arruda, Carla Cardozo Pinto ^{[1
]}

机构：

[1] Univ Fed Mato Grosso Do Sul UFMS, Lab Parasitol Humana, Inst Biociencias, BR-79070900 Campo Grande, Brazil

[2] Univ Fed Mato Grosso Do Sul UFMS, Lab Sintese & Transformacao Moleculas Organ SINTMO, Inst Quim, BR-79074460 Campo Grande, Brazil

[3] Univ Fed Mato Grosso Do Sul UFMS, Lab Imunol Biol Mol & Bioensaios, Inst Biociencias, BR-79070900 Campo Grande, Brazil

[4] Univ Fed Mato Grosso Do Sul UFMS, Lab Biol Mol & Culturas Celulares, Inst Biociencias, BR-79070900 Campo Grande, Brazil

[5] Univ Fed Mato Grosso Do Sul UFMS, Fac Ciencias Farmaceut Alimentos & Nutr, Lab Farmacol & Inflamacao, BR-79074460 Campo Grande, Brazil

[6] Univ Fed Mato Grosso Do Sul UFMS, Inst Quim, BR-79074460 Campo Grande, Brazil

[7] Univ Estadual Mato Grosso Do Sul UEMS, Fac Quim, BR-79804970 Campo Grande, Brazil

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 01期

关键词：

lanthanide complexes; biological activity; Leishmania amazonensis; cytotoxicity; selectivity; mechanism of action; USNIC ACID; CANCER-DIAGNOSIS; DRUG DISCOVERY; PERMEABILITY; CHEMISTRY;

D O I：

10.3390/ijms25010413

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Leishmaniases are neglected diseases with limited therapeutic options. Diffuse cutaneous leishmaniasis can occur in Brazil due to Leishmania amazonensis. This study details the antileishmanial activity and cytotoxicity of complexes of sodium usnate (SAU) with lanthanide ions ([LnL(3) (H2O)(x)] (Ln = La(III), Nd(III), Gd(III), Tb(III), Eu(III) and Sm(III); L = SAU). All lanthanide complexes were highly active and more potent than SAU against L. amazonensis promastigotes and intracellular amastigotes (Pro: IC50 < 1.50 mu M; Ama: IC50 < 7.52 mu M). EuL3<middle dot>3H(2)O and NdL3<middle dot>3H(2)O were the most selective and effective on intracellular amastigotes, with a selectivity index of approximately 7.0. In silico predictions showed no evidence of mutagenicity, tumorigenicity or irritation for all complexes. Treatment with EuL3<middle dot>3H(2)O triggered NO release even at the lowest concentration, indicating NO production as a mechanism of action against the parasite. Incubating promastigotes with the lanthanide complexes, particularly with SmL3<middle dot>4H(2)O and GdL3<middle dot>3H(2)O, led to a change in the mitochondrial membrane potential, indicating the ability of these complexes to target this essential organelle. The same complexes caused cell death through cell membrane disruption, but their relationship with early or late apoptotic processes remains unclear. Thus, the inclusion of lanthanide ions in SAU improves selectivity with a promising mechanism of action targeting the mitochondria.

引用

页数：16

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