Synthesis and biological evaluation of some new mono Mannich bases with piperazines as possible anticancer agents and carbonic anhydrase inhibitors


TUĞRAK M., GÜL H. İ. , Bandow K., Sakagami H., GÜLÇİN İ., ÖZKAY Y., ...More

BIOORGANIC CHEMISTRY, vol.90, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 90
  • Publication Date: 2019
  • Doi Number: 10.1016/j.bioorg.2019.103095
  • Title of Journal : BIOORGANIC CHEMISTRY

Abstract

New mono Mannich bases, (2-(4-hydroxy-3-((4-substituephenylpiperazin-1-yl)methyl)benzylidene)-2,3-dihydro-1H-inden-1-one), were prepared to evaluate their cytotoxic/anticancer properties and also their inhibitory effects on human carbonic anhydrase I and II isoenzymes (hCA I and II). Amine part was changed as [N-phenylpiperazine (1),N-benzylpiperazine (2), 1-(2-fluorophenyl)piperazine (3), 1-(4-fluorophenyl)piperazine (4), 1-(2-methoxyphenyl)piperazine (5)]. The structure of the synthesized compounds was characterized by H-1 NMR, C-13 NMR and HRMS spectra. Cytotoxicity results of the series pointed out that the compound 4 had the highest tumor selectivity value (TS: 59.4) possibly by inducing necrotic cell death in series. Additionally, all compounds synthesized showed a good inhibition profile towards hCA I and II isoenzymes with the Ki values between 29.6 and 58.4 nM and 38.1-69.7 nM, respectively. These values were lower than the reference compound AZA. However, it seems that the compounds 4 and 2 can be considered as lead compounds of CA studies with the lowest Ki values in series for further designs.