Synthesis and anti-HIV activity of steroidal prodrugs of 3'-azido-3'-deoxythymidine (AZT).
A total of seven steroidal prodrugs of AZT were synthesized and tested in vitro for their anti-HIV activity. Three of them were steroidal carboxylic esters prepared from steroidal 17 beta-carboxylic acids and AZT. The remaining four were alkyl steroidal phospho-triesters of AZT. These prodrugs were synthesized using known procedures. Preliminary results of in vitro anti-HIV activity screening showed that all of these prodrugs were active against HIV. While carboxylic esters showed comparable anti-HIV activity to that of AZT, phosphotriesters were less active than AZT. The therapeutic indices of all these prodrugs are comparable to that of AZT.
Balagopala
M I
MI
Department of Chemistry, Florida A. & M. University, Tallahassee 32307, USA.
Ollapally
A P
AP
Lee
H J
HJ
D000737:Androstenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001711:Biotransformation; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000737:Androstenols; D000998:Antiviral Agents; D011355:Prodrugs; C097969:3'-azido-3'-deoxy-5'-O-((11-hydroxy-3-oxo-17-androst-4-enyl)carbonyl)thymidine; D015215:Zidovudine