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

Abstract

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 μM 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.

Keywords:

• Carbonic anhydrase
• chalcone
• cytotoxicity
• Mannich bases
• phenol

Acknowledgements

The authors thank to Tanc M. for his kind assistance during the measuring hCA I and II inhibitions. The authors are thankful to Dr. Murat Sukuroglu (Gazi University, Ankara, Turkey) for HRMS spectra and to Department of Chemistry, Faculty of Science, Ataturk University, Turkey for NMRs spectra.

Declaration of interest

The authors declare that they have no conflict of interest.

Funding

This work was financially supported by Research Foundation of Ataturk University, Erzurum, Turkey (Project Number: 2015-322).

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