Deconstructive Structure-Activity Relationship (SAR) Studies of the Taccalonolides
In collaboration with Dr. April Risinger at UT Health San Antonio, we are developing new synthetic routes to simplified analogs of the taccalonolides as potential new treatments for triple negative breast cancer. Naturally occurring taccalonolides (and semi-synthetic derivatives) are highly complex, steroid-based natural products that have proven microtubule-stabilizing activity that is complementary to the taxanes yet overcome various mechanisms of resistance. As such, they are attractive targets for cancer drug discovery yet their complexity precludes their pre-clinical development beyond academic endeavors. Thanks to funding from the Cancer Prevention and Research Institute of Texas (CPRIT), we have synthesized simplified analogs of the taccas that demonstrate promising cytotoxic profiles against various cancer cells lines. Our continuing efforts are focused on developing new analogs that contain the entire carbon framework of the taccas that are synthetically tractable and exhibit microtubule stabilizing activity relevant to pursue their pre-clinical development.
