Molecular Docking and Microwave Assisted Green Synthesis of Pyrimidine Derivatives as Potential Anti-tubercular Agent

Tuberculosis is one of the leading health problems worldwide. This disease is the leading infectious cause of mortality in current scenario. So, there is urgent need for the development of novel structural classes of anti-tubercular drugs due to emergence of multi-drug resistant strains that are resistant to commonly used drugs. Consequently, the long term treatment protocol is required as a result of resistance and there is always a high probability for the resurgence of disease in the immuno-compromised patients. Recently, various new structural classes of anti-tubercular agents have designed to exhibit promising activity against drug-sensitive and drug-resistant strains of the causative organism Mycobacterium tuberculosis. Based on the concept of bioisosteric similarities with widely used block buster anti-tubercular drug Isoniazid, a series of pyrimidine derivatives are designed. Molecular docking study is performed to determine the binding interactions of the target compounds with the enzyme Mycobacterium tuberculosis enoyl reductase (InhA). The docking results reveal that the binding pose of the selected compounds are energetically favorable and exhibited significant interactions with the active site. The synthesis of pyrimidine derivatives are carried out with the help of microwave irradiation method. This green technology has gained popularity because of greater selectivity to speed up chemical reactions with increase in product yield. Luciferase reporter phage (LRP) assay method is followed to evaluate the antitubercular activity. Some of the tested compounds demonstrated promising anti-tubercular activity in comparison with the standard drug Isoniazid.