No abstract

No abstract

No abstract

No abstract

The (-) enantiomer of gossypol but not the (+) enantiomer had good antiviral activity in peripheral blood mononuclear cells against human immunodeficiency virus type 1 at a concentration more than 20-fold lower than that required for cytotoxicity; however, in H9 cells the (-) enantiomer, although more potent as an antiviral agent, was more cytotoxic.

The nucleoside analogue 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine (d4T, 1) was prepared by ring opening of the 3',5'-anhydro compound 5. This method has been refined such that it can be used to prepare d4T on a large scale. The triphosphate of d4T was also synthesized from 1 in order to examine the mode of action. The in vitro inhibitory activity of d4T was found to be comparable to that of AZT in HIV-infected CEM cells. The triphosphate of d4T (8) and that of AZT inhibited the HIV reverse transcriptase with poly(rA):oligo(dT) as the template:primer with Ki values of 0.032 and 0.007 microM, respectively. The in vitro toxicity of d4T against normal human hematopoietic progenitor cells (CFU-GM) was measured in comparison to AZT. While d4T reduces colony-forming units by 50% at a concentration of 100 microM, it takes only 1 microM AZT to have a similar toxic effect. With erythrocyte burst forming units (BFU-E) the in vitro toxicities for d4T and AZT have comparable ID50 values of 10 and 6.7 microM, respectively.

No abstract

No abstract