Utilisation of efficient reactions to combine moeities exhibiting biological activity to produce novel anti-infectives against HIV and malaria
Chloroquine (CQ) was previously identified as a potential anti-HIV agent and reported to inhibit the production of infectious viral particles at concentrations which are non toxic to human cultured cells. It is speculated that this activity is associated with the decreased production of the heavily glycosylated epitope 2G 12 which is found on the gp120 glycoprotein surface. The hypothesized mechanism involves CQ acting on a range of cellular targets. This work identifies CQ as a lead compound for the discovery of potentially inexpensive drugs and its ability to target cellular enzymes as opposed to viral enzymes may endow the compound with the capacity to oppose resistance. This previous work was the basis of this project and prompted a further investigation into whether the quinoline scaffold is the principal cause of CQ's activity and whether other rationally designed compounds which contain this scaffold would be able to maintain similar or even greater anti-HIV activity. In an attempt to achieve greater activity, the dual drug approach was utilized.
Networked Digital Library of Theses and Dissertations