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Malaria, caused by the plasmodium parasite is an acute febrile illness causing an estimated 219 million cases and 435 thousand deaths in 2017.1 There is need to develop novel antimalarial agents with enhanced properties such as single dose cure potential to counter resistance and sustain efforts towards malaria eradication.
Benzimidazole derivatives have demonstrated encouraging antimalarial properties including a novel mode of action and long predicted human half-lifes, suitable for single dose treatment.2 In this study, the screening strategy and Medicinal Chemistry optimization of N‑Aryl-2-aminobenzimidazoles will be described, highlighting the importance of assessing pharmacological, ADME and DMPK properties both in vitro and in vivo. The work was performed by a consortium of groups and experts from around the globe (Brazil, UK, India, Switzerland and USA) and is lead by a medicinal chemistry team at UNICAMP. The team has successfully delivered analogues with enhanced potency, solubility and reduced hERG channel activity.
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