Investigation of the Anti-human Immunodeficiency Virus Activity of Heteronuclear Bis-isatin Scaffolds Tethered through Propyl and Butyl

A series of novel heteronuclear bis-isatin scaffolds 6a-j tethered through propyl and butyl were designed, synthesized to investigate the influence of the length of the linker between the two isatin motifs and substituents at the isatin framework on the anti-human immunodeficiency virus (HIV) activity against HIV-1(IIIB) (MT-4 cells) in this paper. The synthesized heteronuclear dimers were characterized by H-1-NMR, C-13-NMR, and HRMS. All bis-isatin scaffolds were active against HIV-1(IIIB) with EC50 values ranging from 10.03 to 95.47 mu M and also showed acceptable cytotoxicity towards MT-4 cells. The structure-activity relationship revealed that the length of the linker has great influence on the activity, and the contribution order was butyl > propyl, demonstrating the longer linker was favorable to the activity.