Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT.
 ...
PMID:Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities. 128 69

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.
 ...
PMID:Novel naphthalenedisulfonic acid anti-HIV-1 agents. Synthesis and activity against reverse transcriptase, virus replication and syncytia formation. 172 23