Cathepsin D inhibitors based on tasiamide B derivatives with cell membrane permeability.

Zhi Li, Hang Li, Fan Jiang, Zhaolin Wang, Wei Zhang

Bioorganic & medicinal chemistry 2022 Mar 01

filter terms:

Cathepsin D (Cath D) has been evidenced as a potential target for cancer therapy. Our previous studies revealed that TB-9, a tasiamide B derivative, exhibited highly potent inhibition against Cath D with satisfactory selectivity over Cath E and BACE1. But this compound was inactive on cell level possibly due to poor membrane permeability. Herein, we report the design, synthesis, and evaluation of two novel Cath D inhibitors (2 and 3) which combining tasiamide B scaffold with a cell penetrating peptide (CPP) specifically targeting the endolysosomal compartment. The results revealed that 2 and 3 not only retained highly potent inhibition against Cath D, but also were active against MDA-MB-231 cell lines. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Zhi Li, Hang Li, Fan Jiang, Zhaolin Wang, Wei Zhang. Cathepsin D inhibitors based on tasiamide B derivatives with cell membrane permeability. Bioorganic & medicinal chemistry. 2022 Mar 01;57:116646