Background: Tuberculosis is the leading cause of death, especially among the developing countries. Emerging cases of bacilli drug resistance and its co-infection with HIV have led to an increasing occurrence of treatment failure, which drive the need of new and safe drug, having potent anti-TB activity including the drug resistant strains.Method: In the present study, fifteen novel tetrahydroquinoline based propanehydrazides were designed, synthesized, characterized using spectral techniques (FTIR, 1H NMR, Mass and elemental analysis) and in-vitro evaluated against M. tuberculosis (H37Ra strain). Synthesized compounds were also evaluated for cytotoxicity against human lung fibroblast cells. Conclusion: The result of the anti-tubercular studies revealed that, two compounds 7g and 7o exhibited significant antitubercular activity with MIC values below 20 μg/mL, with safety index greater than 9.94 and 10.57, respectively. Moreover, none of the compounds showed toxicity against lung fibroblast cells at tested concentration of 512 μM. SAR studies of tested compounds revealed that, antitubercular potency of compounds changed significantly with nature and position of the substituent.