Next‐generation antimalarial drugs: hybrid molecules as a new strategy in drug design
Open Access
- 9 December 2009
- journal article
- Published by Wiley in Drug Development Research
- Vol. 71 (1), 20-32
- https://doi.org/10.1002/ddr.20345
Abstract
Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as “covalent bitherapy” involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual‐activity into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next‐generation antimalarial drugs. If the selective toxicity of hybrid prodrugs can be demonstrated in vivo with good bioavailability at the target site in the parasite, it would offer various advantages including dosage compliance, minimized toxicity, ability to design better drug combinations, and cheaper preclinical evaluation while achieving the ultimate object of delaying or circumventing the development of resistance. This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use. Drug Dev Res 71: 20–32, 2010.Keywords
This publication has 57 references indexed in Scilit:
- Artemisinin antimalarials: preserving the “magic bullet”Drug Development Research, 2009
- Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibitionBioorganic & Medicinal Chemistry Letters, 2009
- Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of AgeThe New England Journal of Medicine, 2008
- Evidence of Artemisinin-Resistant Malaria in Western CambodiaThe New England Journal of Medicine, 2008
- Selection of a trioxaquine as an antimalarial drug candidateProceedings of the National Academy of Sciences of the United States of America, 2008
- Design, Synthesis, and Evaluation of 10-N-Substituted Acridones as Novel Chemosensitizers in Plasmodium falciparumAntimicrobial Agents and Chemotherapy, 2007
- Trioxaquines and Heme-Artemisinin Adducts Inhibit the In Vitro Formation of Hemozoin Better than ChloroquineAntimicrobial Agents and Chemotherapy, 2007
- Trioxaquines Are New Antimalarial Agents Active on All Erythrocytic Forms, Including GametocytesAntimicrobial Agents and Chemotherapy, 2007
- A Chloroquine-like Molecule Designed to Reverse Resistance in Plasmodium falciparumJournal of Medicinal Chemistry, 2006
- Artemisinins target the SERCA of Plasmodium falciparumNature, 2003