ABSTRACT The anticancer efficacy of 4‐aryl‐2‐hydrazinothiazole derivatives, which combine a thiazole known for its wide range of medicinal applications and a hydrazide/hydrazone structure known for its unique biological properties, has been determined in numerous studies. In this study, novel 2‐[4‐[(2‐(4‐substituted thiazol‐2‐yl)hydrazono)methyl]phenoxy]acetic acid derivatives (2a–l) were synthesized and evaluated for their anticancer activity in MCF‐7 breast cancer, A549 lung cancer, and L929 normal cell lines using cytotoxicity, apoptosis, and caspase‐3 activation assays. The compounds were found to exhibit high cytotoxicity, particularly showing more selective and high‐potential antiproliferative activity on the MCF‐7 cell line. In apoptosis studies, compounds 2c, 2d, and 2h caused programmed cell death in MCF‐7 cells exceeding 24%, close to cisplatin. Among these compounds, the derivative 2c containing 4‐methoxyphenyl caused caspase‐3 activation at a level similar to cisplatin. To conduct in silico studies of the compounds, molecular docking studies with the (4QTX) caspase‐3 enzyme, molecular dynamics simulation for three compounds (2d, 2g and 2l), and Density Functional Theory (DFT) studies were performed. These studies have shown that the carboxylate groups in the compounds form strong and stable interactions with Arg64 and Arg207.
Zeynep Zişan Demirci, Erol Akgün, G. Çiftçi et al.· Chemical Biology and Drug De...· 0 citations
In this study, 2‐(heteroaryl thio)‐
N
‐(4‐methylthiazol‐2‐yl)acetamide (
3a–3i
) derivatives were synthesized, and the anticancer activity of the compounds were investigated on A549 lung cancer and C6 glioma cell lines. Their anti‐inflammatory activities were tested against COX‐1, COX‐2, and LOX enzymes. Compounds
3a
and
3c
showed high cytotoxic activity against the A549 cell line, while compounds
3b, 3c,
and
3f
exhibited selective cytotoxicity against C6. Compared to cisplatin, a strong antiproliferative activity was detected against the C6 cell line. Further studies of anticancer treatments revealed that compound
3c
significantly induced apoptosis, caspase‐3 activation, and mitochondrial membrane polarization against the A549 cell line. Compound
3c
inhibited COX‐1 by 98.11% and
3h
by 90.47%, while showing no significant inhibition of COX‐2 or LOX. Compound
3c
, a derivative containing 2‐thiazoline, which showed the most potential in terms of both anticancer and anti‐inflammatory activity among all compounds, was subjected to molecular docking studies on Caspase‐3 and COX‐1 enzymes. Compound
3c
was found to interact with Ser205, Arg207, and Gly122 of caspase‐3 enzyme via hydrogen bonds, and similarly, due to its hydrophobic property in both caspase‐3 and COX‐1 enzymes,
3c
interacts with the hydrophobic regions of amino acids.
Dilek Erdaş, A. Evren, Gülşen Akali̇n Çi̇ftçi̇ et al.· ChemistrySelect· 0 citations
