Abstract Cancer is one of the world’s most deadly diseases. According to the American Cancer Society, 2 million people in the US are diagnosed with cancer, and nearly half of the patients died in 2024. Many challenges need to be overcome when treating cancer, such as the destructive effect of long-term treatment and drug resistance. To overcome these problems, the synthesis of 4-oxo-4-(4-(2-oxo-2-(2-(substitutedcarbamothioyl)hydrazinyl)ethoxy)phenyl)butanoic acid derivatives (3a-3f) was designed, and activity studies were performed. Nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) were used for structural analysis. Cytotoxicity studies of the synthesized compounds were carried out on NIH3T3 (non-cancerous mouse embryonic fibroblast), MCF7 (breast cancer), and A549 (human lung carcinoma) cells. The IC50 value of 3e was determined to be 8.495 ± 0.367 µM in A549 cells, and 50.132 ± 0.901 µM in MCF7 cells. In addition, 3e was found to have selective cytotoxic activity against cancer cells, which didn’t cause significant damage to non-cancerous cells. This way, our molecule may be effective on cancer patients without showing any side effects. In silico studies showed that 3e and 3f interacted with the allosteric cavity of the caspase-3 enzyme. Both showed similar localization on the enzyme. Consequently, both compounds have been brought to literature as potential antiproliferative molecules with selective cytotoxicity. GRAPHICAL ABSTRACTMulti-panel figure illustrating molecular structures, flow cytometry data, and interactions between 3e and enzyme.The figure contains four panels. The top left displays a reaction scheme for the transformation of a starting molecule into compound 3e, with chemical structures labeled 3a-3f. The top right shows a flow cytometry plot with FITC-A and SSC-A axes highlighting population distributions P2 (97.02%) and P3 (2.97%). The bottom left features 3D representation of interactions between 3e and enzyme, and the bottom right presents a detailed diagram of interactions among surrounding amino acids and water.
Aybüke Züleyha Kaya, Derya Osmani̇ye, A. Evren et al.· Phosphorus Sulfur and Silico...· 0 citations
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
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