Open Synthesis Network Research in an Undergraduate Laboratory: Development of Benzoxazole Amide Derivatives against Leishmania Parasite

Abstract

An undergraduate laboratory was developed as part of the Drugs for Neglected Diseases initiative's Open Synthesis Network. This activity aimed to develop new compounds efficacious against visceral leishmaniasis. Students successfully synthesized, purified, and characterized ten different benzoxazole amides that were sent for biological testing against several protozoan parasites. Although all the benzoxazole amides had poor activity against L. donovani, several (2, 4, and 9) showed moderate activity against T. cruzi, T. b. rhodesiense, and T. b. brucei paired with low cell cytotoxicity. This drug discovery laboratory activity made a measurable contribution to neglected tropical disease research and was an engaging and research-orientated experience for undergraduate students. Implementation of drug discovery laboratories across a range of student levels and backgrounds is highly achievable using existing laboratory equipment and a short investment in activity preparation and can be a sustainable course component.

A Multidisciplinary Team-Based Classroom Exercise for Small Molecule Drug Discovery

“…1,2 Within the MSc in Drug Discovery at our institution, we realized that we had the opportunity to develop a piece of coursework that drew on the diverse scientific background of the class while teaching all students about the chemistry cycle in detail. Material on drug discovery developed elsewhere has focused on computer-aided drug design, 3,4 on analyzing and designing new compounds, 4,5 on wet laboratory projects 2,6 or on gamification of decision making 7 and has varied in the level of creativity required from the students. We wanted to ensure a high level of student creativity while focusing on the iterative nature of compound optimization and the integration of chemical and biological information.…”