Abstract
A series of six novel cyanopyridine derivatives bearing a 1,3,4-oxadiazole ring have been synthesized and characterized by FTIR, (13)C NMR, (1)H NMR, and elemental analysis. DFT calculations were carried out to determine their molecular geometries, electronic properties, and chemical reactivity. Their cytotoxicity has been evaluated against MCF-7 and CaCo-2 human cancer cell lines using the MTT assay. Most compounds displayed poor cytotoxic activity against the MCF-7 cell line except for compound 4e, which showed potent activity with IC(50) = 8.352 µM. However, the CaCo-2 cell line was highly sensitive toward most tested compounds with an IC(50) range from 2.612 µM to 8.394 µM except for compound 4 d. Molecular docking studies targeting human topoisomerase-IIβ revealed that all compounds exhibited excellent binding affinity within the enzyme's active site, with binding energies ranging from -7.33 to -8.28 kcal/mol. These findings suggest a potential anticancer mechanism underlying the observed cytotoxic activities. All tested compounds revealed low antioxidant activity in the DPPH assay. However, compounds 5b and 5 d presented moderate metal chelating activity. These findings underscore the potential anticancer properties of the synthesized cyanopyridine derivatives.