Modeling of antitubercular activity of biphenyl analogs of 2-nitroimidazo[2,1-b][1,3]oxazine to rationalize their activity profile

The antitubercular activity of ortho-, meta- and para-substituted biphenyl analogs of 2-nitroimidazo[2,1-b][1,3]oxazine has been analyzed through combinatorial protocol in multiple linear regression using physicochemical and structural descriptors obtained from MOE software. The different electronic, hydrophobic, and steric descriptors have been identified for the model development. The study indicates that the ortho substituents with high LUMO (electron acceptor) and less dipole moment are favorable for the activity. The meta and para positions are mainly influenced by steric parameters. Here, the molar refractivity and volume surface area descriptors suggested that the small substituents are conducive for the activity. Also, the para substituents with negatively charged polar surface area are unfavorable for the activity. The identified physicochemical descriptors also indicate the nature of receptor surface in Mycobacterium tuberculosis for this class of compounds. The models and participating descriptors suggest that the substituted biphenyl analogs of 2-nitroimidazo[2,1-b][1,3]oxazine hold scope for further modification in the optimization of antitubercular activity.