Biological evaluation of a novel 1,4-diazine scaffold as potential neuraminidase inhibitors for anticancer and antimicrobial strategies

Development of novel pharmaceutical agents typically starts from an initial hit compound. These initial hits are then optimized using chemical synthesis and then tested for activity. Many active agents are designed based on known starting compounds. These previously identified compounds serve as a starting scaffold on which to make modifications that will improve activity. In this proposal, we plan to investigate novel scaffolds that would allow targeting of a class of enzymes, known as neuraminidases, that are found in humans, bacteria, and viruses. Neuraminidase enzymes cleave terminal sugar residues from glycoproteins in cells and play roles in normal human physiology and disease. The viral neuraminidases are the enzymes targeted by oseltamivir (Tamiflu), which are used as antivirals. Current scaffolds used to target neuraminidase enzymes are synthetically challenging and novel scaffolds could help identify new classes of inhibitors. As part of this proposal, an intern will work in a Canadian laboratory to test a series of compounds they synthesized using a novel scaffold designed to target neuraminidases. In Canada, the intern will learn biochemical assays to validate their compounds against human and bacterial neuraminidase enzymes. Compounds will also be characterized for properties that could indicate their potential for use as pharmaceuticals.

Faculty Supervisor:

Christopher Cairo

Student:

Partner:

Université de Reims Champagne Ardenne

Discipline:

Physics

Sector:

Pharmaceuticals

University:

University of Alberta

Program: