Potential anti-AIDS agents. Synthesis and antiviral activity of naphthalenesulfonic acid derivatives against HIV-1 and HIV-2.
Certain naphthalenesulfonic acid analogues have been synthesized and evaluated for their inhibitory effects on HIV-1- and HIV-2-induced cytopathogenicity, HIV-1 giant cell formation, and HIV-1 reverse transcriptase (RT) activity. A bis(naphthalenedisulfonic acid) derivative having a biphenyl spacer emerged as the most potent and selective inhibitor of virus-induced cytopathogenicity in MT-4 cells. The ED50 values for this compound were 7.6 and 36 microM for HIV-1 and HIV-2, respectively. No toxicity to the host cells was detected at 98 microM. This compound also inhibited giant cell formation and was superseded in potency by a bis(naphthalenedisulfonic acid) derivative having a flexible decamethylene spacer. In the cell-free RT assay, a long-chain amide derivative exhibited the most inhibition of RT. All the compounds that achieved complete inhibition of virus-induced cytopathogenicity at concentrations not toxic to host cells were derivatives of 4-amino-5-hydroxy-2,7- naphthalenedisulfonic acid. These analogues represent new leads for the development of anti-HIV agents.
Mohan
P
P
Department of Medicinal Chemistry and Pharmacognosy (M/C 781), College of Pharmacy, University of Illinois, Chicago 60680.
Singh
R
R
Baba
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007202:Indicators and Reagents; D015394:Molecular Structure; D009282:Naphthalenesulfonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009282:Naphthalenesulfonates; D018894:Reverse Transcriptase Inhibitors