Medicinal chemist, Jane Kelly.
Portland State University Researchers Jane Kelly and Papireddy Kancharla recently received a pair of NIH grants, funding from which will support the continued development of drug candidates for the treatment and prevention of malaria and the treatment of leishmaniasis.
Under Research Professor Jane Kelly's (chemistry) direction, Portland State will lead on a five-year, $3.3 million NIH grant. The project will pursue the late lead optimization of second-generation acridone drug candidates that have shown a remarkable potential to treat and prevent malaria.
Malaria is one of the world's deadliest diseases, with over 200 million cases reported every year and half a million deaths, mostly among young children and pregnant women. And while there are treatments available, increasing drug resistance, the spread of insecticide-resistant vectors and the lack of a clinically effective vaccine are critical problems that underline the urgent need for new therapeutic agents.
For over a decade, Kelly and the research team have been on the leading edge of developing novel compounds to treat and prevent malaria. Their innovations include creating compounds that reverse drug resistance, treat blood- and liver-stage malaria, and tailoring naturally occurring compounds to tackle the disease. Their recent discovery that their compounds address liver-stage malaria could lead to a drug that prevents and cures the fatal disease.
"In the process of developing our acridones to be safer and more potent, we found that they can shut down the parasites in liver cells," Kelly said. "That means that we can potentially stop the disease from even happening."
Building on their previous work, Kelly and the research team, in collaboration with researchers at the Portland Veteran's Hospital and Walter Reed Army Institute of Research, plans to select primary compound candidates from among those they've created by conducting in vitro and in vivo evaluations of the compounds' safety, efficacy, and cross-resistance properties. The goal of the project is to identify the best candidate(s) to advance to pre-clinical trials.
Kelly and co-investigator Papireddy Kancharla also recently received a two-year NIH sub-award, $430,000 under a project lead by OHSU's Scott Landfear. This project aims to identify potential drug candidates to treat Leishmaniasis. This significantly neglected global infectious disease affects millions every year and is a priority of the World Health Organization.
This exploratory research project will test the potency and efficacy of drug-like compounds known as tambjamines against Leishmania parasites. In previous work from Kevin Reynolds, Kelly and Kancharla, the team has demonstrated the effectiveness of tambjamines in combating malaria parasites in vivo. Working with Landfear, Kancharla, a research assistant professor in chemistry and a medicinal chemist with expertise in working with naturally occurring compounds, will design and synthesize novel molecules for testing in Landfear's lab. If the tambjamine compounds demonstrate antileishmanial properties in animal models, the research team plans to submit further grant proposals to carry the work forward.
"This study will allow us to test the compounds in vitro and in vivo settings, and based on our outcomes, we'll know if we have something we can work with or if we'll need to redesign the molecules and pursue further testing," Kancharla said.
The development of these two drug candidates has the potential to save and change millions of lives in developing nations around the globe. According to Kelly, the research team will soon have the data they need to take their compounds to the next stage of pre-clinical testing.