Abstract
AbstractReduced 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.
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