Design and synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer.

Abstract

Novel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6-(4-phenylpiperazin-1-yl)pyridin-3-amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method of the reaction of 2-chloro-5-nitropyridine (1) and N-phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, 1 H NMR, 13 C NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC-3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony-forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases.

• Authors: Serpil Demirci, Taha Bartu Hayal, Binnur Kıratlı, Hatice Burcu Şişli, Selami Demirci, Fikrettin Şahin, Ayşegül Doğan
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 94 Issue 3 Pg. 1584-1595 (09 2019) ISSN: 1747-0285 [Electronic] England
• PMID: 31148379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Cyclin-Dependent Kinase Inhibitor p21
• Piperazines
• RNA
• GAPDH protein, human
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
• Proto-Oncogene Proteins c-mdm2
• Caspases, Effector
• Thiourea
• phenylpiperazine

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis
• Caspases, Effector (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• DNA Fragmentation (drug effects)
• Drug Design
• Drug Screening Assays, Antitumor
• Gene Expression Regulation (drug effects)
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (genetics)
• Humans
• Male
• Molecular Structure
• Piperazines (chemical synthesis, pharmacology)
• Prostatic Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-mdm2 (genetics)
• RNA (metabolism)
• Structure-Activity Relationship
• Thiourea (chemistry)