Daniel L Sun, Soumya Poddar, Roy D Pan, Ethan W Rosser, Evan R Abt, Juno Van Valkenburgh, Thuc M Le, Vincent Lok, Selena P Hernandez, Janet Song, Joanna Li, Aneta Turlik, Xiaohong Chen, Chi-An Cheng, Wei Chen, Christine E Mona, Andreea D Stuparu, Laurent Vergnes, Karen Reue, Robert Damoiseaux, Jeffrey I Zink, Johannes Czernin, Timothy R Donahue, Kendall N Houk, Michael E Jung, Caius G Radu
A potent class of isoquinoline-based α-N-heterocyclic carboxaldehyde thiosemicarbazone (HCT) compounds has been rediscovered; based upon this scaffold, three series of antiproliferative agents were synthesized through iterative rounds of methylation and fluorination modifications, with anticancer activities being potentiated by physiologically relevant levels of copper. The lead compound, HCT-13 , was highly potent against a panel of pancreatic, small cell lung carcinoma, prostate cancer, and leukemia models, with IC50 values in the low-to-mid nanomolar range...
March 1, 2020: RSC Med Chem