The cell wall of () has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites ( and ) and against ESKAPE pathogens. The resultant compounds exhibited varied anti- activity with MIC values in the range of 0.24-31 µM. Cross-screening against and , identified several compounds with antiprotozoal activities in the range of 0.4-20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds , and exhibiting moderate to poor activity against and .