Adrian S Ray, Brenda I Hernandez-Santiago, Judy S Mathew, Eisuke Murakami, Carey Bozeman, Meng-Yu Xie, Ginger E Dutschman, Elizabeth Gullen, Zhenjun Yang, Selwyn Hurwitz, Yung-Chi Cheng, Chung K Chu, Harold McClure, Raymond F Schinazi, Karen S Anderson
To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2',3'-didehydro-2',3'-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain of HIV-1 by 50% at 1.1 +/- 0.1 microM while showing 50% inhibition of cell viability at 84...
May 2005: Antimicrobial Agents and Chemotherapy