Development of Natural Product Derivatives as Antiprotozoal Agents

PROJECT SUMMARYThe proposed research focuses on the development of novel therapeutic agents for the treatment of malaria caused by PfalciparumPreliminary studies have discovered novel natural product and derivative molecules with potent in vitro activity against both sensitive and multidrug resistant malaria strains including a newly emerging artemisinin resistant parasite lineNew compounds are low in toxicity and possess good therapeutic indiceThis SBIR Phase I project aims to obtain proof of concept in vivo PKefficacyand toxicity dataStudies includeIScale up isolation and purification of natural product and synthesis of derivative compoundsIIPharmacokineticPKstudiesIIIIn vivo efficacy studies in SCID mouse Pfalciparum modelIVIn vivo evaluation for acute and sub acute toxicitydevelopmental toxicityand neurotoxicityThe novelty of the project is the discovery of new molecular entitiesThe project involves standard approaches to drug developmentbut the multidisciplinary team that has been assembled will accelerate the generation of preclinical candidates PROJECT NARRATIVEMalaria is one of the most common infectious diseases in the worldIt infectsmillion and kills aboutpeople in a yearThe increasing prevalence of multiple drug resistant strains in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this diseaseThis project focuses on the development of a novel therapeutic agent for preventing and treating Pfalciparum malariaThe novelty of the research is the discovery of new molecular entities