Design, synthesis and biological profiling of aryl piperazine based scaffolds for the management of androgen sensitive prostatic disordersThe authors declare no competing interests. CSIR-CDRI Communication no. 9294.Electronic supplementary information (ESI) available: Experimental details of chemistry and biology, 1H NMR, 13C NMR spectral data, 1H NMR, 13C NMR spectra, HRMS of compounds 8a-e, 9a-n, 11a-b and 12a-g and a representative chromatogram of compound 9a. See DOI: 10.1039/c6md00426a

• Main Authors: Gupta, Sonal, Pandey, Deepti, Mandalapu, Dhanaraju, Bala, Veenu, Sharma, Vikas, Shukla, Mahendra, Yadav, Santosh K, Singh, Nidhi, Jaiswal, Swati, Maikhuri, Jagdamba P, Lal, Jawahar, Siddiqi, Mohammad I, Gupta, Gopal, Sharma, Vishnu L
• Format: Journal Article
• Language: English
• Published: 08.11.2016
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c6md00426a

In the quest for 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 profiles against an androgen sensitive prostate cancer cell line (LNCaP) with EC 50 values of 9.8, 7.6 and 11.2 μM, respectively. These compounds caused a decrease in luciferase activity and a decline in PSA and Ca 2+ levels, which are indicative of their anti-androgenic and α 1A -adrenergic receptor blocking activities, respectively. Compound 9a reduced the prostate weight of rats (47%) and in pharmacokinetic analysis at 10 mg kg −1 it demonstrated an MRT of ∼14 h post dose, exhibiting high levels in prostate. Compound 9a docked in a similar orientation to hydroxyflutamide on an 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 α 1A -blocking activities. Twenty-six piperazine derivatives were synthesized and findings revealed that compound 9a is promising candidate for management of prostatic disorders.