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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 90
  • Publication Date: 2019
  • Doi Number: 10.1016/j.bioorg.2019.103095
  • Journal Name: BIOORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Keywords: Mannich bases, Chalcone, Phenol, Carbonic anhydrase, Cytotoxicity, ERYTHROCYTE ISOZYMES I, CYTOTOXIC ACTIVITIES, HCA I, CORRESPONDING PIPERIDINOLS, ANTIMICROBIAL EVALUATION, THERAPEUTIC APPLICATIONS, ACETYLCHOLINE ESTERASE, ANGELICA-KEISKEI, 1ST SYNTHESIS, DERIVATIVES
  • Anadolu University Affiliated: Yes

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.