Extra precision docking studies of novel luteolin analogues for the inhibition of Tankyrase II: A theoretical-based approach toward novel cancer target

Introduction: Luteolin, a natural flavonoid is known to possess variety of pharmacological activity, particularly growth inhibition. Reports are available to substantiate the interaction of luteolin with tankyrase II, one of the key enzymes responsible for sustenance of telomeres and involved in promoting cellular function. Objective:In our study, we have identified synthetic analogues of luteolin from a chemical compound database (E molecule). After suitable modifications of these analogues, we have screened them for their binding affinity for the active site of tankyrase II (PDB ID: 4HKN). Methods: 15 analogues were subjected to the molecular docking process, which was executed using Glide™ module in Maestro Molecular Modeling platform (version 10.5) from Schrodinger, LLC, using both the standard precision (SP) as well as extra precision (XP) mode. Further, we also attempted to assess the ADME toxicity profiles of the compounds using QikProp application from Schrodinger, LLC. Result: In the present study, we have successfully identified 3 analogues (flav 10, flav 11, flav 12) which exhibited comparable dock scores (-10.02 -10.438 and -10.083 kcal/mol respectively) when compared to the standard luteolin (-11.472). Further, these 3 analogues also demonstrated favourable pharmacokinetic profiles as compared to luteolin. Conclusion: Therefore, the present study will provide insight for further structural modifications and aid in generating a suitable scaffold for enhanced binding affinity to tankyrase II. Future perspectives reside in attempting their synthesis, in vitro and in vivo evaluation to develop a novel anticancer agent.