Research Terms
Researchers at the University of Central Florida have identified new compounds that may treat malaria infections more effectively than current anti-malarial drugs. The malaria parasite, Plasmodium falciparum, has developed resistance to most anti-malarial treatments, including chloroquine and artemisinin. Since the UCF anti-malarial compounds have structures different from current antimalarials, the new compounds may have new cellular targets and have the ability to inhibit the growth of drug-resistant Plasmodium parasites, such as P. falciparum.
Technology 32882
UCF and Florida Atlantic University (FAU) researchers have isolated novel anti-malarial compounds from a library of enriched marine natural products, including cembranoid-type diterpenes, microsclerodermins, dercitamides and bis-indoles. Representative compound, Nortopsentin A, exhibits antiplasmodial activity against P. falciparum chloroquine-resistant Dd2 cells (IC50 0.6 micromole).
Technology 33963
UCF researchers have identified new anti-malarial compounds by 1) screening a library of optimized Aurora kinase inhibitors, and 2) repurposing human Aurora kinase proteins. Aurora kinase is a cell cycle regulatory protein involved in cell growth and development. The identified compounds inhibit the growth of chloroquine-resistant P. falciparum. These potent inhibitors (EC50 < 1 micromole) were identified in cell-based screening using SYBR Green I fluorescence-based assay.
Partnering Opportunity
The research teams are looking for partners to further develop the technologies for commercialization.
Stage of Development
Preclinical.
The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity, American Society for Microbiology, Antimicrobial Agents and Chemotherapy, p. 2362–2364 May 2013 Volume 57 Number 5, doi:10.1128/AAC.02091-12.
Researchers at the University of Central Florida and the University of Oklahoma have identified fungus-derived compounds for developing treatments against drug-resistant species of Plasmodium. Compounds collected from a large library of diverse fungi (including pure compounds and extracts) may enable scientists to target new cellular structures of malaria-causing parasites such as Plasmodium falciparum. The species is resistant to most antimalarial treatments, including chloroquine.
Technical Details
The researchers identified potential antimalarial compounds through cell-based screening of P. falciparum multidrug-resistant strains. The compounds came from a diverse library of fungi found in habitats and ecological niches across the United States. Using the SYBR Green I-based fluorescence assay, the scientists screened the samples for agents with the ability to inhibit intraerythrocytic growth of chloroquine-resistant P. falciparum Dd2. Such agents were either an HDAC inhibitor or a peptaibol. These unique pharmacophores from broad areas of chemical space provide chemical starting points for developing lead compounds of new drugs against malaria.
Partnering Opportunity
The research team is looking for partners to develop the technology further for commercialization.
Stage of Development
Preclinical.
Researchers at the University of Central Florida have developed potent compounds for fighting chloroquine-resistant malaria-causing parasites. The low nanomolar compounds were effective against chloroquine-resistant Dd2 strains of Plasmodium falciparum parasites in vitro and completely cured malaria infection in vivo. The Plasmodium falciparum parasite has developed resistance to most antimalarial treatments, including chloroquine and artemisinin-based combination treatments (ACTs). Additionally, the high cost of ACTs prevents their broad use in low-income malaria-endemic countries and the loss of efficacy of frontline ACTs to the resistant malaria strains underscore the need to boost global malaria eradication efforts.
The UCF invention comprises compounds and pharmaceutical compositions that exhibit antiplasmodium potency against chloroquine-resistant (Dd2) strains of P. falciparum. For example, the most active compounds exhibit an IC50 = 15nM. Also included in the invention are methods of treating or preventing malaria using the antimalarial compounds.
Technical Details
UCF researchers identified several metabolically stable 2-arylvinylquinolines as fast-acting antimalarial agents that kill asexual blood-stage parasites at the trophozoite phase. The compounds show excellent selectivity profiles (RI < 1 and SI > 200). Additionally, the lead compound demonstrates transmission-blocking potential. In murine models, it exhibits exceptional in vivo antimalarial efficacy with 100% reduction of parasitemia without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of compounds for the development of new antimalarial treatments.
Partnering Opportunity
The research team is seeking partners for licensing and/or research collaboration.
Stage of Development
Murine malaria model.
Synthesis, Structure–Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines, J Med Chem. 2020 Oct 22; 63(20): 11756–11785.
The University of Central Florida invention is an anti-malarial compound, a type II kinase inhibitor, with a novel scaffold. The compound exhibits therapeutic and prophylactic properties in animal models and has a favorable pharmacological profile.
