Biodistribution and Anticancer Characteristics of Les-3833, A Novel 4-thiazolidinone-Based Lead Compound

Recently, we identified the promising anticancer potential of the synthetic 4-thiazolidinone-based anticancer lead compound Les-3833 which demonstrated tumor-suppressing action in vitro and in vivo. Based on the results of previous studies, the aim of this research was to investigate the cytotoxicit...

Full description

Saved in:
Bibliographic Details
Published in:Scientia pharmaceutica 2020-06, Vol.88 (2), p.18-12
Main Authors: Kobylinska, Lesya, Lozynskii, Andrii, Lesyk, Roman, Stoika, Rostyslav, Vari, Sandor G
Format: Article
Language:English
Subjects:
4-thiazolidinone derivative
BALB/C mice
biodistribution
Brain research
Cancer
Chromatography
Cytotoxicity
Drug dosages
Health aspects
Kidneys
Laboratories
Lead compounds
Leukemia
Liver
Medical research
Plasma
Studies
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Recently, we identified the promising anticancer potential of the synthetic 4-thiazolidinone-based anticancer lead compound Les-3833 which demonstrated tumor-suppressing action in vitro and in vivo. Based on the results of previous studies, the aim of this research was to investigate the cytotoxicity in vitro and the biodistribution in laboratory mice to support the biotherapeutic drug development of Les-3833. Les-3833 (2.5 mg/kg) was intravenously injected into male Balb/c mice. Measurements were performed at 5 min, 15 min, 1 h, 4 h, and 24 h time points in blood plasma, brain, liver, and kidney using high-performance liquid chromatography/tandem mass spectrometry. After the administration of Les-3833, the maximum level of this compound was observed in plasma at 2.08 min. In the brain, the mean maximum concentration of Les-3833 was 7.17 ng/mL at 5 min, while after 15 min, it was not found. In the liver, at 5 min, the maximum concentration was 1190 ng/g. At 15 min, concentration of Les-3833 in the liver decreased by 14.3%; at 6 h by 22.8%; and after 24 h by 64.7%. Its maximum concentration in kidney was 404 ng/g within 5–15 min, at 1 h it decreased by 36.1%, and after 24 h by 49.3%. Thus, Les-3833 was rapidly taken up by different organs from the bloodstream, partially metabolized in the liver, and excreted mainly through the kidneys, while in the brain, a very low concentration could be observed for only a short period of time.
ISSN:2218-0532
0036-8709
2218-0532
DOI:10.3390/scipharm88020018