Hadeer Nasr, Hager Ismail, Toka Adel, Zeinab Nasr, Alaa Moustafa, Muhammed Ismail, Maria Attallah and Mahmoud Salama Ahmed
Faculty of Pharmacy, The British University in Egypt, Al-Sherouk City Cairo-Suez Desert Road Cairo, Egypt
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, where the epidemiological studies refer to the potential of its increase in the next decade. Generation of tyrosine kinase inhibitors is a novel strategy targeting HCC. Sorafenib is a multi-kinase inhibitor with known activity against tyrosine kinase. A virtual library of 50 ligands possessing Biphenyl urea skeleton was designed, following different strategies, such as chain extension, classical bio-Isosterism, ring opening, and alkyl substitution. This was followed by energy minimization using MMFF94. The whole library was screened via docking along with tyrosine kinase receptor co-crystallized with Sorafenib (PDB ID: 3HEG) using Openeye molecular modeling software, followed by further validation using AutoDock Vina tools. Five ligands showed better binding affinity profile ranges from -10.60 Kcal/mol to -9.00 Kcal/mol, compared to Sorafenib (ΔG= -8.70 Kcal/mol). These results suggest the potential of finding novel analogs to be synthesized targeting tyrosine kinase.