ACTIVITY OF THE (R)-ENANTIOMERS OF 9-(2-PHOSPHONYLMETHOXYPROPYL)-ADENINE AND 9-(2-PHOSPHONYLMETHOXYPROPYL)-2,6-DIAMINOPURINE AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS IN DIFFERENT HUMAN CELL SYSTEMS

The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivati ves of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated fo r their inhibitory effect on HIV replication in several human cell sys tems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP an d PMPA were similar to 10- to 100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PM PA was comparable to that of the prototype acyclic nucleoside phosphon ate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and se lective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 mu M for HIV-1/Ba-L in MIM to 1-2.8 mu M for HIV-1/II IB and HIV-1/HE in C8166, GEM, Molt/4, MT-4 and PBL cells. Both (R)-PM PA and (R)-PMPDAP were not toxic to the host cells at 300 mu M. (C) 19 96 Academic Press, Inc.