Antibiotic/Anticancer Drug Development
Our research leverages the structural diversity of natural products to develop new therapeutic agents. Natural products contain evolutionarily selected motifs with privileged biological activity. We focus on those accessible at scale through fermentation, then chemically degrade them into stereochemically complex building blocks. These are used to create combinatorial libraries that blend natural product-like complexity with the diversity of synthetic chemistry. Libraries are screened to identify initial hits, which are then optimized through medicinal chemistry to advance lead compounds.

Triazolononactate Antibacterials
From the macrocyclic ionophore antibiotic nonactin, we derive nonactic acid via fermentation and degradation. Using nonactic acid as a pharmacophore, we synthesize triazolononactates—a novel antibiotic class active against Gram-positive pathogens, including MRSA and VRE. Current work centers on iterative optimization and identifying the biological target through microbiological and biochemical studies.

Dihydrofolate Reductase Inhibitors
We design inhibitors of dihydrofolate reductase (DHFR), essential for purine, thymidylate, and amino acid synthesis. Building on the clinical precedent of trimethoprim (Bactrim), we are developing analogs to overcome rising resistance. Our long-term collaboration has yielded potent, selective compounds with promise as next-generation antibacterial agents.

Compound Libraries from Complex Bioblocks
Conventional combinatorial libraries often lack the stereochemical and topological complexity characteristic of antibiotics. To address this gap, we generate small, stereochemically rich building blocks from polyethers, terpenes, and alkaloids, assembling novel, natural product-inspired libraries for high-value screening campaigns.

Inhibitors of DNA Methyltransferase I
Targeting epigenetic regulation, we develop selective inhibitors of DNMT-1, the primary maintenance methylase. Using medicinal chemistry, 3D-QSAR, and crystallography, we design isoindolinone-based inhibitors derived from natural scaffolds such as stachybotrymide and porritixin. These compounds aim to reverse hypermethylation, restore normal gene expression, and re-engage apoptotic pathways in cancer cells.