Related Experiment Video

Updated: Oct 16, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
12:03

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy

Published on: September 5, 2016

Structure-activity relationships in platelet-activating factor (PAF). 10. From PAF antagonism to inhibition of HIV-1

N Serradji1, O Bensaid, M Martin

  • 1Unité de Recherche Pharmacochimie Moléculaire et Systèmes Membranaires, Laboratoire de Pharmacochimie Moléculaire, Université Paris, France.

Journal of Medicinal Chemistry
|June 8, 2000
PubMed

Insights

New piperazine derivatives show dual activity against Platelet-Activating Factor (PAF) and HIV replication in brain cells. Compound PMS 601 is a promising candidate for treating HIV-associated dementia (ADC) without cytotoxicity.

Area of Science:

  • Neuroscience
  • Virology
  • Pharmacology

Background:

  • Platelet-Activating Factor (PAF) and macrophage lineage cells contribute to neuronal injury, inflammation, and HIV replication in the central nervous system (CNS), leading to AIDS dementia complex (ADC).
  • PAF receptor antagonists offer potential therapeutic strategies for neurotrauma and related conditions.

Purpose of the Study:

  • To investigate the potential anti-HIV activity of piperazine derivatives designed to inhibit PAF effects.
  • To evaluate the correlation between anti-PAF and anti-HIV activities and identify key structural features for antiviral efficacy.

Main Methods:

  • Synthesis and in vitro testing of piperazine derivatives, including those with carbamate functions.
  • Assessment of anti-PAF and anti-HIV activities in HIV-infected monocyte-derived macrophages (MDM).
  • Evaluation of cytotoxicity and effects on viral enzymes (reverse transcriptase, protease).

Main Results:

  • Piperazine derivatives demonstrated anti-HIV activity in MDM, independent of their anti-PAF effects.
  • The presence of a carbamate group enhanced antiviral activity.
  • Compound PMS 601 exhibited dual activity (anti-PAF and anti-HIV) with IC50 values of 8 and 11 microM, respectively, and showed no cytotoxicity at 1000 microM.
  • PMS 601 did not inhibit acellular reverse transcriptase or protease activity.

Conclusions:

  • Piperazine derivatives, particularly PMS 601, possess significant anti-HIV and anti-PAF activities relevant to CNS pathologies.
  • PMS 601 is a promising dual-acting compound for further investigation in the treatment of HIV-1-associated dementia.
  • Structural modifications, like carbamate presence and lipophilicity, influence antiviral efficacy.

More Related Videos

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader07:13

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Related Concept Videos

Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...