Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases

YAMALI C., GÜL H. İ., Sakagami H., Supuran C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.31, ss.125-131, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1080/14756366.2016.1221825
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.125-131
  • Anahtar Kelimeler: Carbonic anhydrase, chalcone, cytotoxicity, Mannich bases, phenol, CARBONIC-ANHYDRASE, BIOLOGICAL EVALUATION, CYTOTOXICITY, DERIVATIVES, PIPERIDINOLS, INHIBITION, ANTICANCER
  • Atatürk Üniversitesi Adresli: Evet

Özet

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 mu M concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.