Ligand Based Design, ADMET and Molecular Docking Studies of Arylpiperazine Derivatives as Potent Anti-Proliferate Agents Against LNCAP Prostate Cancer Cell Lines

Abstract

Purpose Prostate cancer is the most common non-cutaneous cancer suffered by men and the second leading cause of cancer-related deaths in men. The efficacy of current therapies have been reported to vary from patient to patient and have been accompanied by varying degrees of side effects. This study aimed to design novel compounds with potent cytotoxic activity and lesser toxicity against prostate cancer. Method A Quantitative Structure Activity Relationship (QSAR) model was built to model the cytotoxic activity of arylpiperazine compounds against LNCAP prostate cancer cell line. The built QSAR model was used to design and predict the cytotoxic activity of novel derivatives via the ligand base design. The pharmacokinetic properties of the designed compounds were predicted using the pKCSM tool and their molecular docking interaction with the androgen receptor was investigated using PyRx and Discovery Studio software. Result The QSAR model built had statistical parameters; R 2 \u2009=\u20090.7588, R 2 adj \u2009=\u20090.7014, Q 2 cv \u2009=\u20090.6394 and R 2 ext \u2009=\u20090.6099 which met statistical benchmarks for stable and robust model. 29 new arylpiperazine compounds were designed and 20 were observed to be more potent than the template compound. The ADMET properties of nine compounds were observed to be significantly better than that of the template and were comparable to those of standard drugs apalutamide, bicalutamide and abiraterone. Molecular docking studies revealed that the compounds primarily form electrostatic and hydrophobic interactions with the androgen receptor having a binding affinity of – 7.45 to – 8.80\xa0kcal/mol. Conclusion This study present compounds which show great potential as excellent leads for the design of novel prostate cancer drugs