Analyse et modélisation de nouveaux inhibiteurs non nucléosidiques de la transcriptase inverse du virus de l'immunodéficience humaine de type 1 (VIH-1)

  • Sandro Boland

Student thesis: Doc typesDoctor of Sciences

Abstract

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immune DeficiencySyndrome (AIDS). Treatment of HIV-infected patients is currently based on the use of chemicalcompounds that interfere with various steps of the viral replication cycle (chemotherapy).Although these therapies allow for a significant improvement of a patient's health, theynonetheless remain imperfect and expensive. Research for new and improved anti-HIVcompounds is therefore necessary. This Ph. D. thesis is dedicated to the rational design and analysis of new non nucleosideinhibirors of HIV-1 reverse transcriptase (NNRTI), a key enzyme in HIV lifecycle. Most of thestudied compounds are derived from the 2-pyridinone ring, that is part of several NNRTIfamilies. Rational drug design usually requires a good understanding of the main interactions betweenthe macromolecular target (RT) and its ligands. However, no crystal structure of a RT-pyridinone complex has been reported yet. Our first objective was therefore to build atheoretical model describing RT-pyridinone interactions and providing a better understanding ofstructure-activity relationships among pyridinones. The information obtained in this theoreticalmodel was then used in order to develop new and potent inhibitors.
Date of Award27 Feb 2004
Original languageFrench
Awarding Institution
  • University of Namur
SupervisorFrançois Durant (Supervisor), Jean-Marie Andre (Jury), Laszlo Hevesi (Jury), Johan Wouters (Jury) & Arsène Burny (Jury)

Keywords

  • Antivirals
  • Reverse transcriptase
  • Inhibitor
  • Non-nucleoside
  • Rational drug design
  • Molecular modeling
  • Pharmacophore
  • HIV-1

Cite this

Analyse et modélisation de nouveaux inhibiteurs non nucléosidiques de la transcriptase inverse du virus de l'immunodéficience humaine de type 1 (VIH-1)
Boland, S. (Author). 27 Feb 2004

Student thesis: Doc typesDoctor of Sciences