A New Oxopiperazin-Based Peptidomimetic Molecule Inhibits Prostatic Acid Phosphatase Secretion and Induces Prostate Cancer Cell Apoptosis
| Autor: | Yoni Moskovits, Sharon Ruthstein, Pinchas Zer Aviv, Michael Shokhen, Didier Vertommen, Olga Viskind, Arie Gruzman, Moran Shubely, Amnon Albeck |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Signal peptide Peptidomimetic General Chemistry Biology medicine.disease 03 medical and health sciences Prostate cancer 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Prostatic acid phosphatase Biochemistry Prostate 030220 oncology & carcinogenesis LNCaP Cancer research medicine Cytotoxic T cell Secretion |
| Zdroj: | ChemistrySelect. 1:4658-4667 |
| ISSN: | 2365-6549 |
| DOI: | 10.1002/slct.201600987 |
| Popis: | Reduced Prostatic acid Phosphatase (PAcP) secretion is associated with inhibition of the proliferation rate of prostate cancer cells. Signal peptidase 1 (SPase 1) is the main protease that cleaves the signal peptide of secretory proteins and allows their secretion. Thus, we hypothesised that inhibition of SPase 1 might lead to an antiproliferative effect in prostate cancer cells. Using homology computer modelling, we created a human SPase 1 model. With this model we designed and synthesised four novel (S)-3-(4-aminobutyl)piperazin-2-one-based peptidomimetics. The in vitro cytotoxic activity of these compounds was evaluated in the Lymph Node Carcinoma of the Prostate (LNCaP) cancer cell line. Indeed, (S)-(3-(2-(4-(((benzyloxy)carbonyl)amino)butyl)-4-(3-methoxy-3-oxopropyl)-3-oxopiperazin-1-yl)propyl)boronic acid, compound 8) reduced PAcP secretion, as well as exhibited significant cytotoxic effect in LNAcP cells. As reported in this study, an antiprostate cancer drug development approach, which is based on inhibiting PAcP secretion, is innovative and it might serve as source for developing novel antiprostate cancer drugs. |
| Databáze: | OpenAIRE |
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