Design, Synthesis, and Anticancer Activity Evaluation of Hydrazone/Thiazole Hybrids Against A549 Cell Line via Intrinsic Apoptotic Pathways

Authors:
Publisher website
Google Scholar
Abstract
In this study, we have designed ten novel 2‐[1‐[2‐(4‐(substituted phenyl)thiazol‐2‐yl)hydrazono]ethyl]‐4‐nitrophenol ( 2a–2j ) derivatives bearing hydrazone group and thiazole moiety. Target compounds are synthesized via two simple and affordable steps starting from 2‐hydroxy‐5‐nitroacetophenone. Structural confirmation of the resulted compounds performed by APCI‐MS (atmospheric‐pressure chemical ionization mass spectrometer), HRMS (high‐resolution mass spectrometry), 1 H and 13 C NMR (nuclear magnetic resonance) and melting point apparatus. Cyclooxygenase (COX) inhibition of the compounds performed. Anticancer activity of the compounds investigated with apoptosis induction, mitochondrial membrane polarization (ΔΨm), caspase‐3 activity tests. The results of the cytotoxicity assay indicated that compounds 2c , 2e , and 2i exhibited cytotoxic activity comparable to that of cisplatin. Based on the cytotoxicity test results compounds 2c, 2e, 2g, 2h, and 2i selected to performed further investigations. Apoptosis results exhibited that 2c, 2g , and 2i had higher apoptotic induction (early and late apoptosis) rates in A549 cells. Furthermore, 2c showed cisplatin‐like mitochondrial activity at 13.46%. Also, 2c showed notable caspase‐3 enzyme activation on A549 cells. In silico studies indicated that compound 2c interacts with the allosteric cavity of caspase‐3. The findings from the anticancer activity studies suggest that compound 2c may induce cell death through the intrinsic apoptotic pathway.
Funding Information
  • Anadolu Üniversitesi (2203S014)

This publication has 54 references indexed in Scilit: