Anticancer activities of novel Mannich bases against prostate cancer cells

Demirci S., DEMİRBAŞ N.

MEDICINAL CHEMISTRY RESEARCH, vol.28, no.11, pp.1945-1958, 2019 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 11
  • Publication Date: 2019
  • Doi Number: 10.1007/s00044-019-02426-1
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.1945-1958


This study was designed to synthesize hybridizing molecules starting from compound of 6-(4-phenyl-piperazin-1-yl)pyridine-3-ylamine by enhancing its biological activity with other heterocycles and to determine anticancer activity of the resulting compounds. To this end, 6-(4-phenylpiperazin-1-yl)pyridin-3-ylamine (4) was used as the leading compound, which is known to exert anticancer activities. The synthesis of the leading compound was carried out using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method with the reaction of N-phenylpiperazine (2) and 2-chloro-5-nitropyridine. 6-(4-phenylpiperazin-1-yl)pyridin-3-ylamine (4) was converted to compound 5, an active intermediate compound, by substitution of one of the amine hydrogens with ethyl bromoacetate. The resulting ester product (5) followed by the hydrazidation (6) was added arylisocyanate to obtain the active intermediate (8). Then, by a series of substitution through cyclization and condensation reactions, thiazolidinone (9), 1,3,4-oxadiazole (7), and 1,2,4-triazole (10) were synthesized. Novel Mannich bases (11a-11f and 12a-12f) were obtained using oxazole (7) and triazole (10) hetero rings with primer or secondary amine compounds. The characterization of the compounds was completed using FT IR, H-1-NMR, C-13-NMR, HRMS spectroscopic methods and elemental analysis technique. The chemicals, then, were tested for their anticancer activities against prostate cancer cell lines PC3 [ATCC, CRL-1435], LNCaP [ATCC, CRL-1740], and DU145 [ATCC, HTB-81]. The results revealed that the Mannich bases exhibited moderate cytotoxic activity against cancer cells tested.