Table of Contents
Metal-Based Drugs
Volume 2 (1995), Issue 3, Pages 143-151
http://dx.doi.org/10.1155/MBD.1995.143

Use of Organosilicon Compounds towards the Rational Design of Antiparasitic and Antiviral Drugs

Bioorganic Chemistry Laboratory, University of Bordeaux 2, Bordeaux F-33076, France

Received 5 January 1995; Accepted 14 February 1995

Copyright © 1995 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

One of the major problems met for the conception of antiviral or antiparasitic drugs is to reach a high level of selectivity towards the pathogenic agent versus the host. We shall describe two synthetic approaches where main group organometallics have been used towards this goal. A series of nucleoside sila-analogues was synthesized as potential therapeutic agents designed to inhibit HIV Reverse Transcriptase. In a second approach novel organosilicon derivatives have been synthesized as mimics of antisense oligonucleotides.

Infectious agents, namely viruses or parasites, more or less use cellular machinery. Therefore therapeutic agents must interfere with biochemical mechanisms or possess high affinity towards specific molecular cellular components, to reach selectivity.

We thought that main group organometallics could show many advantages for designing biologically active molecules in this field. They allow a high synthetic flexibility for the modulations of physico-chemical properties and they show a mechanistic behaviour which may be close to the one of several heteroelements present in living organisms such as sulfur or phosphorus.

We tried to use this approach towards two directions involving the synthesis of organosilicon derivatives i.e:

-the synthesis of organosilicon derivatives as inhibitors of HIV Reverse Transcriptase,

-the synthesis of organosilicon precursors of modified antisense oligonucleotides.