title: Novel naphthalenedisulfonic acid anti-HIV-1 agents. Synthesis and activity against reverse transcriptase, virus replication and syncytia formation.
abstract: Several naphthalenedisulfonic acid derivatives have been synthesized and evaluated in four anti-HIV-1 screens. Antiviral activity was evaluated in the assays that measure inhibition of HIV-1 reverse transcriptase (RT), HIV-1 induced giant cell (syncytia) formation, and HIV-1 induced cytopathogenicity in both a laboratory and clinical strain of HIV-1. 4-acetylamino-5-hydroxy-2,7- naphthalenedisulfonic and a bis naphthalenedisulfonic acid derivative emerged as the most active compounds exhibiting activity in all assays at concentrations non-toxic to the host cells. The bis 3-amino-1,5-naphthalenedisulfonic acid derivative was the most active compound, but less active than the bis 4-amino-5-hydroxynaphthalenedisulfonic acid analog in the assays that measure RT and syncytia inhibition. However, in the assay that measured inhibition of cytopathogenicity in a clinical HIV-1 isolate, 4-acetylamino-5-hydroxy-2,7-naphthalenedisulfonic acid was the most potent analog, demonstrating an in vitro therapeutic index greater than 54. This study shows that for certain naphthalenedisulfonic acid moieties a bis derivative is not a requirement for significant anti-HIV-1 activity. These agents represent a new class of lead non-nucleoside anti-HIV-1 compounds worthy of further development for potential anti-AIDS therapy.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60680.
authors.forename: P
authors.initials: P
authors.lastname: Mohan
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: M
authors.initials: M
authors.lastname: Baba
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D015726:Giant Cells / Q000187:drug effects* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D009282:Naphthalenesulfonates / Q000138:chemical synthesis / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009282:Naphthalenesulfonates; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase