A novel pseudo-five-component synthesis, molecular docking analysis, ADMET and drug likeness studies of new 3,4-dihydro-2H-pyrrole derivatives as potent HIF-1α inhibitors.

New poly-substituted 3,4-dihydro-2H-pyrrole derivatives were synthesized via a novel one-pot pseudo-five-component reaction in fairly high yields (68-85%). The structures of the products were elucidated from their FT-IR, 1H NMR, 13C NMR and mass spectral data. A NOESY experiment was used to verify the stereochemistry of the single stereoisomer resolved from the reaction mixture. Insights into vibrations, geometry and energetics of the products were obtained using DFT calculations. Given the well-established role of the HIF-1α protein in breast cancer progression, its active site was selected for molecular docking studies. The products demonstrated favorable binding scores (ranging from -9.4 to -10.5 kcal mol-1) and specific interactions with amino acid residues within the active pocket of HIF-1α. Drug-likeness predictions reveal that the products adhere to Lipinski's rules and none of them trigger pan-assay interference, suggesting their potential as candidates for further development. In silico ADMET profiling for the products exhibited promising properties across critical parameters. The synthesized products are promising candidates for subsequent in vitro evaluation as potential HIF-1α inhibitors.