Drug Discovery Group

The Drug Discovery Group (DDG) is an ambitious enterprise, focused on the design and synthesis of innovative therapeutics for the treatment of grievous illness.

DDG projects are driven by Synthetic Organic Chemistry but inspired by Molecular Biology. We draw from both disciplines in equal measure to engineer novel drug candidates targeting cancer and antibiotic-resistant infection. We conduct much of our organic syntheses on the surface of polymeric beads, which minimizes chemical waste and purification steps. Our project designs are modular, allowing separate teams to create components, which we assemble into finished drug candidates.  Our workflow follows an endless cycle of conception, execution, and reporting- with opportunities to contribute at each stage.

Current Project:

Solid-Phase Synthesis of Cephalosporin Dual Ligands with Anticancer and Antibiotic Activity

Cephalosporin analogs are established components of the Antibody-Directed Enzyme Prodrug Therapy (ADEPT) strategy for selectively targeting tumors with cytotoxic drugs (1). On cleavage with antibody-linked b-lactamase, cephalosporin-prodrug conjugates 1 (Figure-1) release cytotoxic drugs proximal to tumors. Synthesis of a polymer-supported, orthogonally-protected derivative of 1 is our key short-term goal. Scaffolds like 1 are derived from 7-aminocephalosporanic acid, which is inexpensive and readily available. Once we achieve this milestone, we will install prodrugs with known anticancer and antibiotic activity.

Figure-1: The ADEPT strategy for prodrug delivery to tumors.

(1) Therapeutic Potential of Prodrugs Towards Targeted Drug Delivery Abhinav P. Mishra*, Suresh Chandra, Ruchi Tiwari, Ashish Srivastava and Gaurav Tiwari: The Open Medicinal Chemistry Journal 2018, 12, 111-123.

Affiliated Investigators:

Richard Connors                         [email protected]