Low Cost Drugs for Treating Patients Suffering from Drug Resistant Malaria
Section: For Industry
Categories: "Viruses, Chronic & Infectious Diseases"
Reference #: 2008-002
OTC Contact: Blaine Hackman, Ph.D. (Directory Information | Send a Message)
Description
Georgetown University is seeking a partner interested in the development and commercialization of novel antimalarial drugs for treating drug resistant strains of malaria. Researchers have discovered new derivatives of chloroquine that are effective against drug resistant strains of plasmodium falcipram (FCP), the most lethal of the malaria strains. These compounds were potent against drug resistant strains of malaria, while maintaining antimalarial activity against drug sensitive malaria strains. Furthermore, these compounds are easy and inexpensive to synthesize, making them especially appealing for manufacture and distribution in impoverished regions that are most in need of antimalarial therapeutics. These compounds represent a potential breakthrough in treating all strains of malaria, while improving access to the cutting edge of malaria drugs in the developing world.
Applications
This technology encompasses new low cost, small molecule antimalarial drugs for the treatment and prevention of drug resistant malaria infections in humans.Advantages
- These compounds are responsive to both drug resistant and drug sensitive malaria strains.
- Chloroquine derived drugs are inexpensive to synthesize, for example, the commercial cost of chloroquine is $1.07/g, compared to $500/g for artemisinin.
- New therapies, such as artemisinin, are showing decreasing efficacy in fighting malaria in some regions, so there is an increasing demand for new potent antimalarial drugs.
Stage of Development
Rational design was used to guide the synthesis of chloroquine (CQ) derivatives for screening against both chloroquine sensitive (CQS) and chloroquine resistant (CQR) strains of malaria. Researchers specifically focused on the modification of the CQ side-chain in their syntheses, while maintaining the 4-amino-7-chloroqunoline core. For example, CQ side-chain length and functional groups were among the parameters that were varied. Exemplary compounds of the invention have shown IC50 values in the nanomolar range against the CQR strain Dd2 and the CQS strain HB3, suggesting these compounds are promising new leads for combating both CQS and CQR strains of malaria.Relevant Publications
“Overcoming Drug Resistance to Antimalarials by Systemic Side Chain Variation of 7-Chloro-4-aminoquinolines.” J. Med. Chem. 2008, 51, 1995-1998.
“4-N¬, 4-S, and 4-O-Chlroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pK¬¬a on Activity vs. Chloroquine Resistant Malaria”. J. Med. Chem. 2008, 51, 3466-3479.
“Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas.” Bioorg. Med. Chem. 2009, 17, 270-283.
Patent Status
Patents are currently pending covering both compositions and methods of use
