The Yoganathan laboratory provides an interdisciplinary teaching and research environment for both graduate and undergraduate students. Research projects in our laboratory fall into three major areas: (1) Development of efficient and atom-economical synthetic methodologies to discover novel therapeutic leads. (2) Development of chemical tools to better understand biological processes that are linked to various human diseases. (3) Investigation of structure activity relationship (SAR) of complex natural products, and evaluation of their pharmacological properties to improve the efficacy of new drug-like natural products.
We actively collaborate with pharmacologists, chemical biologists, biochemists and toxicologists to investigate various aspects of our research projects. The multi-disciplinary research environment provides our students exposure and training in many different scientific fields.
1. Design, synthesis and development of benzimidazoles as small molecule therapeutic agents: Benzimidazole is a privileged scaffold in medicinal chemistry and has been extensively utilized in clinically available drugs and in drug leads being developed for the treatment of various diseases. We have recently developed simple and scalable synthetic methodologies to access structurally diverse benzimidazoles. The library of compounds we have generated allowed us to investigate their biological properties against various diseases, including bacterial infections, and cancer. More recently, we have identified a series of benzimidazoles as useful leads that promote bone remodeling and wound healing. These small molecules modulate Bone Morphogenetic Protein Receptor (BMPR) signaling. Barasa, L.; Yoganathan, S.* RSC Adv. 2018, 8, 35824-35830. Barasa, L.; Vemana, H.; Surubhotla, N.; Ha, S. S.; Kong, J.; Yong, A.; Croft, J. L.; Dukhande, V.*; Yoganathan, S.* Anti-Cancer Agents Med. Chem.2020, 20, 301-314. Barasa, L.; Yong, A.; Yoganathan, S.* ChemistrySelect, 2020, 5, 3173-3178. Najafi, S.; Barasa, L.; Huang, S. Y.; Yoganathan, S.*; Perron, J. C.* Scientific Reports, 2022, 12, 12146. Najafi, S.; Barasa, L.; Frianela, J. M. J.; Alkhamisy, J. H.; Yoganathan, S.; Perron, J. C. Front. Biosci. (Landmark Ed.), 2023, 28, 268.
2. Chemical synthesis of siderophore analogs and evaluation of their biological activities: Sioderophores are small molecule secondary metabolites produced by microorganisms under iron limiting environment. These molecules bind to ferric ion effectively and assist in iron acquisition via dedicated siderophore transporter systems. Siderophores have been exploited as useful leads in antibiotic development, however their anticancer potential has not been extensively explored. Our lab is using a medicinal chemistry approach to synthesize and evaluate siderophore analogs as potential anticancer agents. Our goal is also to collaborate with experts in cancer pharmacology to understand the mechanism of anticancer activity of these compounds.
3. Chemical synthesis of phenolic natural product analogs and evaluation of their biological activities: Polyphenols or phenolic acids are structurally and biologically interesting natural products. They are often associated with considerable health benefits due to their inherent anti-oxidant properties. These popular class of natural products are found in variety of fruits and other plant components. Resveratrol found in the skin of grapes and curcumin in turmeric are two of the classical examples all of us are familiar with. Our lab is synthesizing structural analogs of a simple phenolic acid that mimic the structure of a natural product called 'alpha-mangostin' and resveratrol for medicinal chemistry studies. From our initial evaluation, we have identified two new compounds with single digit micromolar IC50 values against different types of cancer cell lines. Our current efforts are focused on structure optimization and investigation of the mechanism of anticancer activity.