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

• Published in: Chemical biology & drug design 2019-09, Vol.94 (3), p.1584-1595
• Main Authors: Demirci, Serpil, Hayal, Taha Bartu, Kıratlı, Binnur, Şişli, Hatice Burcu, Demirci, Selami, Şahin, Fikrettin, Doğan, Ayşegül
• Format: Article
• Language: English
• Subjects: antitumor activity; apoptosis; cell cycle; DNA fragmentation; thiazolidinone; thiourea
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.13575

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, 1H NMR, 13C 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. Phenylpiperazine derivative blocks cell proliferation of prostate cancer (PC) cell lines. Phenylpiperazine derivative caused cell cycle arrest of PC cell lines. Phenylpiperazine derivative might be a potential anticancer agent for PC.