Design, synthesis, biological evaluation, structure-activity relationship, and toxicity of clinafloxacin-azole conjugates as novel antitubercular agents

Abstract Based on the advantages of azole molecules and fluoroquinolone drugs, we designed and synthesized 34 clinafloxacin-azole conjugates using fragment-based drug design and drug combination principles. The in vitro activities of the synthesized conjugates against Mycobacterium tuberculosis (H37Rv), Hela cell as well as Gram-positive and Gram-negative bacteria were assayed. The bio assay results revealed that most of the target molecules had anti-tuberculosis (anti-TB) activity, of which 14 compounds had very strong anti-TB activity [minimum inhibitory concentration (MIC)  TM2l exhibited the strongest anti-TB activity (MIC = 0.29 μM), low antibacterial activity, negligible toxicity, and good drug-likeness values, which can be considered as an ideal lead molecule for future optimization.