Chapter One - The hybrid antimalarial approach: A roadmap: 2024

Abstract

The continued emergence of drug-resistant strains of Plasmodium spp. has necessitated the exploration of new strategies to counter the ever-rising challenge of containment of human deaths due to malaria. Thus, on the one hand, the scientific and pharmaceutical communities have been trying to enhance the effectiveness of the conventional methods as well as by developing effective vaccines, on the other hand, there has been a continuous quest to find more productive alternatives to the traditional chemotherapeutic agents that are capable of combating multi-drug resistant parasite strains and are superior to the currently most effective “Artemisinin-based Combination Therapies (ACT).” In this context, the design strategy involving the hybridization of two or more active pharmacophores into a single chemical entity has culminated in “The hybrid antimalarial approach” that has drawn inspiration from the successful lead generation against the deadly diseases such as cancer and AIDS. Thus, several chemical classes of hybrid antimalarial drugs have been designed, with the potential advantages in terms of lower toxicity, better pharmacokinetics, dual mode of action and easier formulation, etc. However, a lot needs to be done by the scientific community in designing and synthesizing ideal candidates for progression to the late stages of clinical development. In the chapter, we have the pros and cons of the titled approach and a road map for future developments in this area of investigation.