Insights into the pharmacology of new heterocycles embedded with oxopyrrolidine rings: DNA binding, molecular docking, and anticancer studies

In quest to develop effective anticancer drugs, a series of twelve heterocycles (1 − 12) embedded with oxopyrrolidine rings was synthesized. The compounds (1-12) were characterized by microanalysis, FT-IR, UV-Vis and 1H NMR spectroscopy, and mass spectrometry. Experimental DNA binding and computational docking studies were carried out to identify the biological targets of 1-12. The values of DNA binding constants of 1-12 ranged from 1.5 × 104 to 4.0 × 105 M− 1. The docking energies of the DNA-compound adducts varied from − 23.84 to − 30.96 kJ/mol, and the adducts were stabilized by H-bonding and hydrophobic attractions. The compounds preferred to enter minor grooves of DNA during adduct formation. Cytotoxicity studies of 1-12 were carried out towards both cancerous and normal cell lines. Compounds 4, 6, 7, 8, 9, 10, 11 and 12 at 1.0 nM concentration exhibited good anticancer activities with cell viabilities in the range of 19-110% against breast (MCF-7) and microglial (BV-2) cancer cell lines. The potency of 1-12 as future anticancer agents was ascertained by drug likeness using Lipinski's rule of five. It was observed that 1-12 obeyed the 'Rule of Five' with logP values < 5 and HBAs ≤ 7. All the results taken together indicated good pharmacological properties of the prepared heterocycles, and thus their further biological evaluation towards other cancer cell lines is warranted.