Inhibition of human immunodeficiency virus type (HIV-1) replication by some diversely functionalized spirocyclopropyl derivatives.
Inhibition of HIV-1 replication by differently substituted spirocyclopropyl compounds has been evaluated. Compound 21 showed a moderate activity (EC50 ranging from 2.3 to 5.8 micrograms/ml) against different HIV-1 strains (IIIB, RF, NDK, and an AZT-resistant strain) in different cell lines (MT-4 and C-8166 cells), while it was cytotoxic at 77.7 micrograms/ml, resulting in a selectivity index of 34. This compound was inactive against HIV-2 (ROD) and SIV (MAC251). From "time-of-addition" experiments compound 21, like AZT, appeared to inhibit HIV-1 at the reverse transcriptase step.
Witvrouw
M
M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Pannecouque
C
C
De Clercq
E
E
Fernández-Alvarez
E
E
Marco
J L
JL
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D003521:Cyclopropanes; D013141:Spiro Compounds