Molecular docking based approach for the design of novel flavone analogues as inhibitor of beta-hydroxyacyl-ACP dehydratase HadAB complex

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis and millions of people are suffering with this disease. Drug resistance has further worsened the situation by decreasing the potency of the drug regimen. Overcoming the resistance problem has been a challenging task for the researchers. Currently the drug regimen followed for tuberculosis contains first line and second line drugs but resistance towards some of these drugs is reducing their efficacy towards Mycobacterium. As per the reported literature flavones have been found to be active against Mycobacterium tuberculosis. In the present research work we have tried to design few flavones analogues using molecular modelling software. The 3-dimensional structure of 4RLT was retrieved from the Protein Data Bank, prepared and docked with designed flavones using Schrodinger software. The protein contained bound flavone and molecules were docked at that particular site only to compare the interaction between ligand and residue. About fifteen flavone molecules were docked against beta-hydroxyacyl-ACP dehydratase HadAB complex. Flavone m and flavone k showed the best binding affinity with good docking score. These molecules can be considered a good candidate for further structural modification, synthesis and evaluation.