Sulphated Sugar Alpha-Cyclodextrin Sulphate, a Uniquely Potent Anti-HIV Agent, Also Exhibits Marked Synergism with AZT, and Lymphoproliferative Activity

Abstract

Sulphated sugars, alpha-cyclodextrin sulphate (A-CDS), sodium pentosan polysulphate (PPS), and beta-cyclodextrin sulphate (B-CDS) were evaluated for their inhibitory effect on the replication of human immunodeficiency virus (HIV-1) in normal human peripheral blood mononuclear cells (PMNCs). All three drugs had potent anti-HIV activity, A-CDS being the most potent. A-CDS, PPS and B-CDS were also tested for their direct inhibitory effect on reverse transcriptase (RT) in vitro. PPS inhibited the RT reaction at 4.0 μg ml−1 and above whereas B-CDS and A-CDS did not. The drugs were not cytotoxic up to 100 μg ml−1 and also showed significant lymphoproliferative activities. PPS and B-CDS exhibited higher lymphoproliferative activity than A-CDS. A-CDS, B-CDS, and PPS showed profound antiviral synergism with AZT. An additive anti-HIV effect, rather than a synergestic effect, was observed between the sulphated sugars. Thus, these sulphated sugars, because of their nontoxic nature, lymphoproliferative activity and anti-HIV activity at low concentrations, may be valuable chemotherapeutic agents in the treatment of AIDS. In particular, A-CDS, because of its marked anti-HIV synergism with AZT (which would lower the required dose of AZT in vivo), could result in an efficacious and essentially nontoxic combination chemotherapy for AIDS.