Synthesis of activity-based protein profiling probes for malaria and hypertension disease models & potential novel ACE inhibitors with an attenuated zinc binding group

Abstract

Angiotensin-converting enzyme (ACE) and P. falciparum A M1 (PfA-M1) are both zinc metalloproteases implicated in hypertension and malaria, respectively. Hypertension affects approximately 26 % of the world’s population while each year over 300 million cases of malaria occur worldwide resulting in between 1.5 and 2.7 million deaths annually. Hypertension treatment with current ACE inhibitors is marred by unpleasant side effects, such as cough and angioedema. In malaria, the parasites continuously develop resistance to anti-malarial drugs where the disease is endemic. There is therefore a need for continuous research into the application of new techniques as well as the design of new small molecule chemical entities as probes or chemotherapeutic agents.