MOLECULAR DOCKING STUDY OF SIX PYRIMIDINE DERIVATIVES AS EGFR (EPIDERMAL GROWTH FACTOR RECEPTOR) AND CA IX (CARBONIC ANHYDRASE IX) INHIBITOR
Objective: The present study was carried out to discover whether these pyrimidine derivatives have the potential to be used as epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA) IX inhibitors through structure-based in silico study.
Methods: Docking was performed on 6 pyrimidine analogs; cetuximab and curcumin were taken as reference drug. The structure of the target protein retrieved from the RCSB Protein databank and the protein-ligand docking was performed using Pyrx AutoDock wizard with MGL tools 1.5.6 by using Lamarckian algorithm.
Results: All the compounds have shown lower binding energy and inhibition constant (Ki) value than reference drug cetuximab and curcumin. Out of the 6 inhibitors analyzed vkh has shown minimum binding energy against the target protein EGFR and CA IX respectively. Smaller Ki value shows stronger interaction. The scoring value of the interaction of vkh i. e-10.74 and-9.93 Kcal/mol and Ki 13.17ɳM and 53.04ɳM against the target protein EGFR and CA IX respectively while the reference drug cetuximab has shown binding energy-6.09 Kcal/mol with Ki value 34.44 µM and curcumin has shown binding energy-6.02 kcal/mol with Ki value 38.60 µM.
Conclusion: It can be concluded that the molecule vkh could have potential to be used as an EGFR inhibitor and CA IX inhibitor.
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