Tuberculosis is an age-old debilitating infectious disease caused by the microbe Mycobacterium tuberculosis. Despite the efforts made by international community, this ancient scourge could not contain. Lipid rich cell wall, very active resistance development mechanisms and ability to switch to a quiescent stage inside the host tissues made anti TB drug development a formidable challenge. It has been more than three decades for the introduction of new drug in the anti TB category (except bedaquiline suggested for MDR/XDR TB in 2014). Thioridazine, an antipsychotic drug recognized recently for its efficacy in the treatment of MDRTB patients. This has opened new possibilities for repurposing/repositioning as a potential means of identifying effective drugs for persistent diseases like tuberculosis. We screened DrugBank database containing 1552 FDA approved small molecules using ligand shape based virtual screening protocol of vROCS software. Amongst the top 500 hits obtained by using Tanimoto COMBO score, 20 drugs were selectedand had screened for in vitro antitubercular activity against MTB H37Rv. From our study most potent antitubercular activity (MIC) was observed in sertraline (1.62 μg/mL) followed by nortriptyline (3.12 μg/mL), amitryptiline (6.25 μg/mL), fluoxetine (6.25 μg/mL), fluoxamine (6.25 μg/mL), sulconazole (6.25μg/mL), olanzapine (12.5 μg/mL), mianserine (12.5 μg/mL) and diphenhydramine (25 μg/ml).