Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations.
Muhammad Babar TajAhmad RaheelRabia AyubAfnan M AlnajeebiMatokah AbualnajaAlaa Hamed HabibWalla AlelwaniSadia NoorSami UllahAbdullah G Al-SehemiRahime ŞimşekNouf Abubakr BabteenHeba AlshaterPublished in: PloS one (2023)
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 (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human 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 the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed 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.
Keyphrases
- molecular docking
- molecular dynamics simulations
- dna damage
- structure activity relationship
- density functional theory
- oxidative stress
- human serum albumin
- human health
- signaling pathway
- molecular dynamics
- endoplasmic reticulum stress
- computed tomography
- cell cycle arrest
- machine learning
- dna repair
- deep learning
- pet ct