Background: Recently, researchers have been warning about the increased mortality of
the various cancer types. Also, the lung adenocarcinoma and the glioma types are burning issues for
world's health due to late or wrong diagnosis and/or insufficient treatment methods. For this
purpose, our research group designed and synthesized novel 4,5-dimethyl thiazole-hydrazone
derivatives which were tested against cancer and normal cell lines to understand the structureactivity
Methods: The lead compounds were obtained by reacting 2-(substituted aryl-2-ylmethylene)
hydrazin-1-carbothioamide with 3-chloro-2-butanone derivatives. The structural elucidation of the
compounds was performed by 1
C-NMR, and LC/MS-IT-TOF spectral and elemental
analyses. The synthesized compounds were tested in vitro for the anticancer activity against A549
human lung adenocarcinoma and C6 rat glioma cells and investigated for which pathway to induce
cell death. Also, the docking study of the active compounds was achieved to understand the SAR.
Results: The targeted compounds (2a-2l) were synthesized successfully above 70% yields, and
the analysis findings proved their purity. In general, the results of activity studies displayed
significant effects against at least one cell line, except compounds 2e (indol-3-yl) and 2h
(4-dimethylaminophenyl). Furthermore, compounds 2b and 2f displayed potential anticancer
activity. With the help of molecular docking study, a potential selectivity of compound 2f was
observed for type II protein kinase. On the other hand, compound 2b interacted with the active site
nearly the same as Dasatinib. Therefore, these two compounds could be used as a base on
developing selective anticancer drugs.
Conclusion: Pyridin-2-yl (2b) derivative was found to be a favorable molecule with high anticancer
potency against C6 and A549 cell lines. Additionally, 1-naphthyl (2f) derivative was a worthy
compound for potential selectivity. In future studies, it will be our priority to focus on developing
derivatives of these two compounds (2b and 2f) and elucidate their mechanisms.