Background:
Cancer disease is making a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or act synergistically with the existing chemotherapeutics.
Objective:
Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazoles resulting in a better pharmacophore for anticancer activity.
Methods:
A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines.
Results:
The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control IC50 in the range of 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed compounds were stabilized by hydrogen bond and π-π interactions with the protein.
Conclusion:
The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is preliminary and needs further studies to take the synthesized compounds to the next level in the cancer research field.
Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking
