当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES期刊下所有文献 > In vitro anti-Leishmania activity of T6 synthetic compound encapsulated in yeast-derived β-(1,3)-d-glucan particles.

In vitro anti-Leishmania activity of T6 synthetic compound encapsulated in yeast-derived β-(1,3)-d-glucan particles.

Abstract：

:The objective of this study was to encapsulate a synthetic compound, the 4-[(2E)-N'-(2,2'-bithienyl-5-methylene)hydra-zinecarbonyl]-6,7-dihydro-1-phenyl-1H-pyrazolo[3,4-d]pyridazin-7-one (T6) in glucan-rich particles mainly composed by the cell wall of Saccharomyces cerevisiae (GPs) and to study their individual and combined activity on Leishmania infantum. The possible mechanism of action of T6 was also investigated. Our results showed the activity of T6 compound in both promastigote (IC50 = 2.5 μg/mL) and intracellular amastigote (IC50 = 1.23 μg/mL) forms. We also found activity against intracellular amastigote forms (IC50 = 8.20 μg/mL) when the T6 compound was encapsulated in GPs. Another interesting finding was the fact that T6 encapsulated in GPs showed a significant decrease in J774A1 macrophage toxicity (CC50 ≥ 18.53 μg/mL) compared to the T6 compound alone (IC50 = 2.27 μg/mL). Through electron microscopy and biochemical methodologies, we verified that the activity of T6 in promastigote forms of L. infantum was characterized by events of cell death by apoptosis like increased ROS production, cell shrinkage, phosphatidylserine exposure and DNA fragmentation. We conclude that T6 can be considered a promising anti-Leishmania compound, and that the use of GPs for drug encapsulation is an interesting approach to the development of new effective and less toxic formulations.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Volpato H,Scariot DB,Soares EFP,Jacomini AP,Rosa FA,Sarragiotto MH,Ueda-Nakamura T,Rubira AF,Pereira GM,Manadas R,Leitão AJ,Borges O,Nakamura CV,Sousa MDC

doi

10.1016/j.ijbiomac.2018.08.019

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

1264-1275

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(18)31666-0

journal_volume

119

pub_type

杂志文章

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