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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.

antiviral chemistry and chemotherapy

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