Twelve　novel　propylene-tethered　ciprofloxacin-isatin　hybrids　3a-f　and　4a-f　were　designed,　synthesized　and　characterized　by　MS,　HRMS,　1H　NMR　and　13C　NMR.　All　hybrids　were　evaluated　for　their　in　vitro　antimicrobial　activities　against　representative　Gram-positive,　Gram-negative　and　mycobacterial　pathogens,　cytotoxicity　in　VERO　cell　line　as　well　as　metabolic　stability　and　in　vivo　pharmacokinetic　(PK)　properties.　The　preliminary　results　indicated　that　all　mono-isatin-ciprofloxacin　hybrids　exhibited　excellent　antibacterial　activities　with　MIC　ranging　from　≤0.03　to　0.5　μg/mL　against　most　of　the　tested　strains.　In　particular,　ciprofloxacin-isatin　hybrid　3d　was　highly　potent　against　all　tested　Gram-positive　and　Gram-negative　strains　including　clinically　important　drug-resistant　pathogens,　which　was　comparable　to　or　more　potent　than　the　parent　ciprofloxacin　and　reference　levofloxacin.　Whereas,　conjugate　3b　(MIC:　0.10　and　0.5　μg/mL)　was　4-　and　8-fold　more　active　than　ciprofloxacin　(MIC:　0.78　μg/mL)　and　rifampicin　(MIC:　0.39　μg/mL)　against　MTB　H37Rv,　and　4->256　times　more　potent　than　the　three　references　ciprofloxacin　(MIC:　2.0　μg/mL),　rifampicin　(MIC:　32　μg/mL)　and　isoniazid　(>128　μg/mL)　against　MDR-TB.　Both　hybrid　3b　and　3d　with　low　cytotoxicity　(CC50:　64　and　256　μg/mL)　also　showed　acceptable　metabolic　stability　and　in　vivo　PK　properties,　could　act　as　leads　for　further　optimization.　©　2018　Elsevier　Masson　SAS