Isoquinoline thiosemicarbazone displays potent anticancer activity with in vivo efficacy against aggressive leukemias.

ABSTRACT: 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. Density functional theory (DFT) calculations showed that fluorination at the 6-position of HCT-13 was beneficial for ligand-copper complex formation, stability, and ease of metal-center reduction. Through a ch

SUBMITTER: Sun DL 

PROVIDER: S-EPMC7593890 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature