The 3,4,5-trimethoxyphenyl motif is a common structural feature of a number of natural occurring antimitotic agents, especially those capable interacting with microtubules such as the cis-stilbene, combrestatin A-4. Chalcones possessing this pharmacophore have likewise been demonstrated to exhibit a diverse range of biological actions including anticancer, anti-invasive, antioxidant, and anti-inflammatory activities. As part of an experiential learning experience in academic drug discovery termed WSU PharmaFlights, so-called flights of 6-10 molecules based on a particular biologically relevant structural pattern on the privileged chalcone scaffold are to be designed, synthesized, and spectroscopically characterized as a starting point for lead-development with potential biological collaborators. In this paradigm, students are assigned a specific pharmacophore group on either ring A or B of the chalcone nucleus, assess the scope of activities associated with that fragment and propose fragments on the alternate ring likely to produce enhanced or dual function activity against certain therapeutic or diagnostic targets. This specific project involves the rational design of a flight of chalcones displaying the 3,4,5-trimethoxyphenyl moiety on ring B, and a discussion of the potential applications of this lead discovery library.
Fourman, C. (2018). PharmaFlights: Fragment based drug discovery based on chalcones with a 3,4,5-trimethoxy substitution on ring B. Wright State University, Dayton, Ohio.