Abstract
Novel azole derivatives 3–30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good β-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G1 and G2/M phase of the cell cycle and induced apoptotic activity by increasing sub-G1 phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and BAX/BCL-2 ratio expression that resulted in increasing the active caspase 3/7 percentages and trigger apoptosis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
