Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations

Abstract

Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound5a, 5c, 5d, 5e, 5g, 5h, 5i,and5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (againsthuman serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the5bcompound showed the lowest ΔET (2.29 eV) while 5ishowed relatively highest βtot (69.89 x 10–31 esu), highest αave (3.18 x 10–23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells.