A　new　set　of　tetraethylene　glycol　tethered　ciprofloxacin–isatin　hybrids　5a–l　with　greater　lipophilicity　than　the　parent　ciprofloxacin　was　designed,　synthesized,　and　screened　for　their　in　vitro　antimycobacterial　activity　against　drug-sensitive　Mycobacterium　tuberculosis　(MTB)　H　37　Rv　and　multidrug-resistant　MTB　strains　as　well　as　toxicity　in　a　mammalian　VERO　cell　line.　The　preliminary　results　revealed　that　all　hybrids　exhibited　considerable　activity　against　MTB　H　37　Rv　with　minimum　inhibitory　concentration　in　a　range　of　0.205–14.186 μg/mL.　Especially,　hybrid　5a　with　low　cytotoxicity　displayed　highest　activity　against　both　drug-sensitive　MTB　H　37　Rv　and　two　clinically　isolates　multidrug-resistant　MTB　strains,　suggesting　that　it　may　serve　as　a　new　and　promising　candidate　for　further　study.　©　2018　Wiley　Periodicals,　Inc.