Abstract:
A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring
demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was
to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-
{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid
(Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-
one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity,
caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant
defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung
carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nm to 100 µM) of
the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell
lines was induced by both compounds at a concentration range from 10 to 100 µM. Both compounds
decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and β-actin in
the BJ cells. Interestingly, a significant decrease in the level of NF-κB gene and protein expression was
detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of
inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere
with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.
