Last update 01 Nov 2024

RT x HIV Ribonuclease H x HIV-1 protease

Last update 01 Nov 2024

Basic Info

Related Targets

RTHIV Ribonuclease HHIV-1 protease

Drugs associated with RT x HIV Ribonuclease H x HIV-1 protease

SP-1093V

Target

HIV Ribonuclease H x HIV-1 protease x RT

Mechanism

HIV Ribonuclease H inhibitors [+2]

Active Org.-

Originator Org.

McGill University

Active Indication-

Inactive Indication

HIV Infections

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RT x HIV Ribonuclease H x HIV-1 protease

100 Translational Medicine associated with RT x HIV Ribonuclease H x HIV-1 protease

0 Patents (Medical) associated with RT x HIV Ribonuclease H x HIV-1 protease

Literatures (Medical) associated with RT x HIV Ribonuclease H x HIV-1 protease

01 Sep 2009·Medicinal ChemistryQ4 · MEDICINE

Inhibition of HIV-1 Ribonuclease H Activity by Novel Frangula-Emodine Derivatives

Q4 · MEDICINE

Article

Author: Giovanni, Floris ; Cheng, Yung-Chi ; Luca, Zinzula ; Tatyana, Kharlamova ; Ginger, E. Dutschman ; Francesca, Esposito ; Enzo, Tramontano

The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) activity hydrolyzes the RNA component of the viral heteroduplex RNA:DNA replication intermediate. Even though this function is essential for viral replication, until now only very few compounds have been reported to inhibit it. Anthraquinones are common secondary metabolites which have diverse biological activities. In particular, some of them have been reported to inhibit the HIV-1 RT polymerase and integrase activities in biochemical assays. Given the structural similarities between integrase and RNase H proteins, we synthesized a series of frangula-emodine derivatives and showed that the introduction of a bromine atom in position 7 of the anthraquinone structure leads to derivatives which are able to inhibit both HIV-1 polymerase and RNase H functions at micromolar concentrations. Mechanism of action studies performed on the 7-brom-6-capital O, Cyrillic-phenacyl-1,8-dihydroxy-3-methyl anthraquinone (K67) showed that this compound is a non-competitive inhibitor of the RNase H function and that it binds to a site which is not overlapping to the non-nucleoside RT inhibitors binding site. This study demonstrates that anthraquinone derivatives may be a scaffold to be further developed to obtain selective HIV-1 RNase H inhibitors and represent a new step toward the identification of new anti-RT agents.

01 Jan 1998·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

Dicaffeoylquinic and Dicaffeoyltartaric Acids Are Selective Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

Q2 · MEDICINE

Article

Author: Hostomsky, Zdenek ; Robinson, W. Edward ; McDougall, Brenda ; King, Peter J. ; Reinecke, Manfred G. ; Wu, Bor Wen

ABSTRACTCurrent pharmacological agents for human immunodeficiency virus (HIV) infection include drugs targeted against HIV reverse transcriptase and HIV protease. An understudied therapeutic target is HIV integrase, an essential enzyme that mediates integration of the HIV genome into the host chromosome. The dicaffeoylquinic acids (DCQAs) and the dicaffeoyltartaric acids (DCTAs) have potent activity against HIV integrase in vitro and prevent HIV replication in tissue culture. However, their specificity against HIV integrase in cell culture has been questioned. Thus, the ability of the DCQAs and DCTAs to inhibit binding of HIV type 1 (HIV-1) gp120 to CD4 and their activities against HIV-1 reverse transcriptase and HIV RNase H were studied. The DCQAs and DCTAs inhibited HIV-1 integrase at concentrations between 150 and 840 nM. They inhibited HIV replication at concentrations between 2 and 12 μM. Their activity against reverse transcriptase ranged from 7 μM to greater than 100 μM. Concentrations that inhibited gp120 binding to CD4 exceeded 80 μM. None of the compounds blocked HIV-1 RNase H by 50% at concentrations exceeding 80 μM. Furthermore, when the effects of the DCTAs on reverse transcription in acutely infected cells were measured, they were found to have no activity. Therefore, the DCQAs and DCTAs exhibit >10- to >100-fold specificity for HIV integrase, and their activity against integrase in biochemical assays is consistent with their observed anti-HIV activity in tissue culture. Thus, the DCQAs and DCTAs are a potentially important class of HIV inhibitors that act at a site distinct from that of current HIV therapeutic agents.

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