1. Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells.
- Author
-
Nepali K, Lin MH, Chao MW, Peng SJ, Hsu KC, Eight Lin T, Chen MC, Lai MJ, Pan SL, and Liou JP
- Subjects
- Amides chemistry, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, HSP90 Heat-Shock Proteins metabolism, Humans, Male, Models, Molecular, Molecular Structure, PC-3 Cells, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Quinolines chemistry, Resorcinols chemistry, Structure-Activity Relationship, Tumor Cells, Cultured, Amides pharmacology, Antineoplastic Agents pharmacology, HSP90 Heat-Shock Proteins antagonists & inhibitors, Prostatic Neoplasms drug therapy, Quinolines pharmacology, Resorcinols pharmacology
- Abstract
The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF