Chalcones from the deep: in silico medicinal chemistry and quantum chemical insights into their anticancer and anti-HIV potency

Chalcones obtained from marine sources have become significant frameworks in the discovery of potential innovative therapies. This work thoroughly explored a library of over 100 chalcones for their dual anticancer and anti-HIV potential using combined quantum chemistry and molecular modeling methodologies. DFT simulations at the B3LYP-D3/6-31+G(d) level included HOMO–LUMO, DOS, ESP mapping, and NBO. Molecular docking conducted against two targets, epidermal growth factor receptor (EGFR, PDB ID: 1NQL ) and HIV-II protease (PDB ID: 1HSG ), revealed the significance of chalcones ( C-1 , C-3 , C-6 , and C-9 ), confirming robust binding affinities (up to −9.48 kcal/mol). MD simulations confirmed the structural integrity of the ligand-protein complexes. To substantiate the computational methods, DFT-derived NMR and IR spectra of an analogue of C-6 (phlorizin) were compared with experimental data, demonstrating remarkable concordance and affirming the theoretical framework. The results underscore the potential of marine chalcones as dual-action therapeutic agents for cancer and HIV therapy. • More than one hundred chalcones were optimized, among which the top ten with the best binding energy were screened. • DFT approach was utilized to ascertain the quantum characteristics using the B3LYP-D3/6-31+G(d) theoretical framework. • Pharmacokinetic profiles of screened chalcones were evaluated. • Molecular docking and simulations were employed to explore the structure-activity relationship and interactions.