Optimizing the resveratrol fragments for novel in silico hepatocellular carcinoma de novo drug design

Abstract

Abstract Hepatocellular carcinoma (HCC) incidence varies widely around the world and is impacted by factors such as the prevalence of chronic hepatitis B and C infections, alcohol intake, and access to healthcare. The proteins (BRAF_human, VGFR3_human, EGFR_human and UFO_human) play a vital role in hepatocellular carcinoma prognosis, which involves cell proliferation, cell growth, transmission of extracellular signals to the cell nucleus and consequently regulating many other cellular processes. Fostamatinib has been studied for its possible use in the treatment of hepatocellular cancer because it is a more convenient therapy choice for patients and has minor side effects on the human body. However, resveratrol phytochemical has been investigated for its potential use in the prevention and treatment of a wide range of disorders, including cancer, cardiovascular disease, diabetes, and neurological problems due to its frequently antioxidant, anti-inflammatory, and immune-modulating characteristics, which can aid in the prevention of chronic illnesses. This study developed de novo-based fragment-optimized resveratrol (FOR), enhancing therapeutic potential and lowering toxicity. The docking study was performed with four target proteins, and the findings reveal that the vascular endothelial growth factor receptor 3 protein possessed the highest binding energy values of −7.6 kcal/mol with FOR. Additionally, it completely fulfills the criteria of drug-likeliness rules. Thus, FOR proves to be an efficient drug candidate for future in-vivo studies against hepatocellular carcinoma.

Keywords

• Hepatocellulular cancer
• Resveratrol
• ADME
• De novo drug
• Fragment optimization