New anti-HIV agents, cyclodextrin-3'-azido-3'-deoxythymidine (CD-AZT) conjugates, were synthesized and characterized. A succinate diester spacer was used to covalently couple 3'-azido-3'-deoxythymidine (AZT) onto cyclodextrin. In addition, their sulfates were prepared by the reaction of CD-AZT conjugates and a sulfur trioxide/pyridine complex at 80 degrees C. The degree of AZT substitution of the synthesized conjugates and the sulfur contents of their sulfates were calculated from elemental analysis and ranged from 1.3 to 4.7 and from 8.4 to 12.1, respectively. These resulting sulfated conjugates were expected to have a synergistic effect against HIV because of the two anti-HIV active agents (sulfate group and AZT) by the inhibition of virus attachment to cells and that of reverse transcriptase. The in vitro antiviral activity of these conjugates was determined and used to evaluate the potential applications in anti-AIDS drugs. The in vitro anti-HIV activities indicated that the synthesized conjugates and their sulfates against HIV-1 and HIV-2 strains were much better inhibitors than AZT. (c) 2005 Wiley Periodicals, Inc.