New AZT analogues having 5'-alkylsulfonyl groups: synthesis and anti-HIV activity.
New derivatives of azidothymidine (AZT) substituted by alkyl and alkylsulphonyl groups at N-3 and C-5', respectively, have been synthesized. The new synthesized derivatives showed remarkable anti-HIV-1 and HIV-2 activity in MT-4 cells. Compounds 8 and 10 have IC(50) values of 0.83 and 0.31 microg/mL against HIV-1 with therapeutic index of 83 and 403, respectively, and IC(50) values of 0.93 and 0.29 microg/mL against HIV-2 with therapeutic index of 74 and 431, respectively. This means that compounds 8 and 10 were cytotoxic to MT-4 cells at CC(50) of 69.2 microg/mL and 125 microg/mL, respectively.
Al-Masoudi
Najim A
NA
Fachbereich Chemie, Universität Konstanz, Konstanz, Germany. najim@al-masoudi.de
Al-Soud
Yaseen A
YA
Ali
Ibrahim A I
IA
Schuppler
Thilo
T
Pannecouque
Christoph
C
De Clercq
Erik
E
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004345:Drug Industry / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D010766:Phosphorylation; D013696:Temperature; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015215:Zidovudine