Di‐isatin heteronuclear compounds and their antibacterial activity

Abstract Twenty propylene and butylene tethered di‐isatin heteronuclear compounds 5a‐t were synthesized, and their antibacterial activities were evaluated. Most of the synthesized di‐isatin heteronuclear derivatives were active against both Gram‐positive and Gram‐negative strains, and some of them exhibited considerable activities against drug‐resistant organisms. In particular, di‐isatin 5a (MIC: 32‐512 μg/mL) was more active than the reference vancomycin against Gram‐negative pathogens, demonstrating the antibacterial potential of di‐isatin heteronuclear compounds. The inhibitory activity of di‐isatin 5a was higher than mono‐isatin against Escherichia coli DNA gyrase, suggesting the dimers could improve the inhibitory activity against DNA gyrase when compared with the isatin. The structure‐activity relationship was discussed to provide an insight for rational designs of more efficient antibacterial candidates.