Maya Ruth Thom Fernando

Maya Fernando

Summary of Milwaukee Institute for Drug Discovery (MIDD) research assistantship

The goals for the Fall 2025 semester:

• Work towards synthesizing a library of over 50 benzodiazepine analogues to understand how different structural features affect binding activity at multiple G-protein coupled receptors (GPCR’s).
• Characterize all synthesized compounds by nuclear magnetic resonance (NMR), high pressure liquid chromatography-mass spectrometry (HPLC-MS), chiral chromatography and solubility.
• Determine cytotoxicity in human kidney cells.
• Determine adverse central nervous system effects using rotarod and open field studies in mice.
• Understand the functional activity of lead compounds at receptors of interest, including the Alpha2 and 5-HT2 receptors, through the psychoactive drug screening program (PDSP).
• Use molecular operative environment (MOE) to understand how our lead compounds are interacting with the receptors of interest.
• Optimize a synthesis method to retain stereochemistry of the compounds.

Personal Statement:

I am very grateful to the Milwaukee Institute of Drug Discovery for supporting my research during this semester. This opportunity allowed me to synthesize many new analogues to continue our work on developing benzodiazepines for use at different GPCR’s. With the results from these new compounds, some lead compounds were able to be determined, which are now being tested for the potential to treat pulmonary arterial hypertension. This assistantship also allowed me to work with a group of an undergraduate student and a visiting master’s student. I am thankful for the experience of mentoring a small team and am very appreciative of their contributions.

Undergraduate Student: Shaun Harrington

I've been working in the Arnold Group under Maya's supervision since the end of my sophomore year at UWM. My work focuses on the synthesis and development of novel ligands targeting receptors in the central nervous system. Through this project I've learned about metal-catalyzed cross-coupling reactions and helped develop a large library of benzodiazepine-based analogs, some of which have shown promising antagonistic behavior towards the 5-hydroxytryptamine 2B receptor. This research focuses on modifying a well-known class of compounds to target receptors outside of their traditional scope, with the hope of developing more selective and safe drugs. This project also introduced me to more advanced organic chemistry techniques, such as NMR spectroscopy, liquid chromatography-mass spectrometry, flash column chromatography, and solubility assays. Collaborating with Maya and the Arnold Group has set me up for success as I transition into graduate school to continue doing research.