Design, synthesis and biological profiling of aryl piperazine based scaffolds for the management of androgen sensitive prostatic disorders

MedChemComm
2016.0

Abstract

In the quest of novel scaffolds for the management of androgen sensitive prostatic disorders like prostate cancer and benign prostatic hyperplasia, a series of twenty-six aryl/heteroaryl piperazine derivatives have been described. Three compounds 8a, 8c and 9a exhibited good activity profile against androgen sensitive prostate cancer cell line (LNCaP) with EC50 values of 9.8, 7.6 and 11.2 µM, respectively. These compounds caused a decrease in luciferase activity and decline in the PSA and Ca2+ levels, which are indicative of its anti-androgenic and α1A-adrenergic receptor blocking activities, respectively. Compound 9a reduced prostatic weights of rat (47%) and in pharmacokinetic analysis at 10 mg/kg it demonstrated an MRT of ~14 h post dose, exhibiting high levels in prostate. Compound 9a docked in a similar orientation as hydroxyflutamide on androgen receptor and showed strong π-π interactions. These findings reveal that compound 9a is a promising candidate for management of prostatic disorders with anti-androgenic and α1A-blocking activities.

Knowledge Graph

Similar Paper

Design, synthesis and biological profiling of aryl piperazine based scaffolds for the management of androgen sensitive prostatic disorders
MedChemComm 2016.0
Novel aryl piperazines for alleviation of ‘andropause’ associated prostatic disorders and depression
European Journal of Medicinal Chemistry 2017.0
Synthesis and biological evaluation of arylpiperazine derivatives as potential anti-prostate cancer agents
Bioorganic & Medicinal Chemistry 2019.0
Synthesis, biological evaluation and SAR of naftopidil-based arylpiperazine derivatives
Bioorganic & Medicinal Chemistry Letters 2018.0
Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety
Bioorganic & Medicinal Chemistry 2019.0
Design, synthesis and biological evaluation of novel 3-oxo-4-oxa-5α-androst-17β-amide derivatives as dual 5α-reductase inhibitors and androgen receptor antagonists
Bioorganic & Medicinal Chemistry Letters 2017.0
17(E)-Picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies
Bioorganic & Medicinal Chemistry 2013.0
Quinazoline based α 1 -adrenoreceptor antagonists with potent antiproliferative activity in human prostate cancer cell lines
European Journal of Medicinal Chemistry 2017.0
Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line
European Journal of Medicinal Chemistry 2016.0
Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors
Bioorganic & Medicinal Chemistry 2016.0