In silico investigation of novel sorafenib analogues as potential inhibitors of VEGFR kinase and c-RAF kinase

Abstract

Cancer is the second most prevalent reason for mortality. Researching new drugs to fight cancer is a priority for many research teams due to the lack of specificity in present therapies. Developing target-specific anti-cancer drugs improves therapeutic potency and safety. Also, Computational chemistry play an important role in the research of new possible medicines. Thus, the goal of present research, was to determine in silico studies using the molecular docking and ADME profiling on three newly designed Sorafenib analogues against tyrosine kinase and c-Raf kinase inhibitor enzymes. Molecular docking studies were conducted using PDB ids 2XIR and 3OMV. The Autodock-4 software was utilised for this purpose. Additionally, software tools such as SwissADME and Pro-TOX were employed to perform physiochemical studies and predict toxicity. Molecular docking results showed that compounds (1-3) had strong binding energies of -10.23, -10.24, and -11.39 kcal/mol with VEGFR (PDB Id: 2XIR), while Sorafenib had -11.49; and the energies for c-Raf (PDB Id: 2OMV) were -9.41, -9.48, and -10.89, respectively with reference standard to Sorafenib was -10.39 kcal/mol. It was concluded that compound 3 showed the similar affinity to inhibit VEGFR and c-Raf kinase. It proved by both docking study, molecular dynamic simulation, ADME and tox properties evaluation.

Keywords

• Sorafenib
• anticancer
• c-Raf kinase
• in silico
• ADMET
• molecular dynamic simulation

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