Wainberg MA, Stern M, Martel R, Belleau B, Soudeyns H; International Conference on AIDS.

Int Conf AIDS. 1989 Jun 4-9; 5: 552 (abstract no. M.C.P.63).

IAF Biochem International Inc. Lavel, Quebec, Canada

OBJECTIVE: To test a number of nucleoside analogs in which the 3' carbon of the pentose is replaced by an S or O atom. METHODS: Cpds. were assayed for anti-HIV-1 activity (RT, p24 Ag, cell viability) in T-cell lines (H-9, MT-4) and a monocyte/macrophage cell line (U-937). RESULTS: The lead cpd. NGPB-21 (base = cyt, 3' = S) had a therapeutic index approximately = 1000 (sim. to AZT) and, unlike AZT, had no cell toxicity at therapeutic concs. Also, NGPB-21 was very active in the HIV-1 infected U-937 cell line. Rats given NGPB-21 at 100 mg/kg p.o. daily for 14 days showed no inhibition of body growth, and had normal organ wts. (liver, spleen, testis, kidney) and hematologic profile. Rats given NGPB-21 at 200 mg/kg p.o. readily absorbed the drug and had peak blood levels at 1.5 hr. and t1/2 approximately = 1.0hr. Another cyt analog (DDIII30A) in which 3' = 0 and the sugar-base linkage is in the unnatural alpha-configuration showed a favorable therapeutic index in vitro. CONCLUSION: NGPB-21 and DDIII30A are novel nucleosides showing high potential as anti-AIDS drugs.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Anti-HIV Agents
• Cell Line
• HIV-1
• In Vitro
• Male
• Monocytes
• Rats
• T-Lymphocytes
• Zidovudine
• pharmacokinetics
• reverse transcriptase, Human immunodeficiency virus 1
• toxicity

Other ID:

• 00286889

UI: 102178770

From Meeting Abstracts