Pyridine-based chalcones as promising anticancer agents: Design, synthesis and in silico studies

A novel class of chalcones were synthesized via the Claisen-Schmidt condensation of 6-chloropyridine-3-carbaldhyde with various ortho, meta, and para substituted acetophenones in the presence of a base and a polar protic solvent. The newly synthesized compounds were characterized by using various spectral techniques 1H NMR, 13C NMR, FT-IR, and mass spectroscopy methods. All newly synthesized compounds were evaluated in vitro for anticancer activity against the Human Breast Cancer Cell Line MDA-MB-231, and antioxidant activity was quantified using the DPPH free radical scavenging technique. The anticancer screening findings revealed that the synthesized compounds 3a, 3d, 3e, 3f, and 3j had GI50 of < 10 μg/mL. The compounds 3a and 3j have showed excellent antioxidant activity. Molecular docking simulations have been done against inhibitor of the human estrogen receptor alpha enzyme (PDB ID: 2iog) found that compounds 3a, 3d, 3e, 3f, and 3j have a high binding energy (−7.8 to −8.8 Kcal/mol). The in silico ADME properties of the synthesized compounds (3a-3j) demonstrated that they are very good oral bioavailability medications.