New phenolic Mannich bases with piperazines and their bioactivities

Abstract

In this study, new Mannich bases, 2-(4-hydroxy-3-methoxy-5-((substitutedpiperazin-1-yl)methyl)benzylidene)-2,3-dihydro-1H-inden-1-one (1, 2, 4, 5, 8), 2-(3-((substituted)piperazin-1-yl)methyl)-4-hydroxy-5-methoxybenzylidene)-2,3-dihydro-1H-inden-1-one (3, 6, 7) were synthesized with the reaction of vanilin derived chalcone compound (2-(4-hydroxy-3-methoxybenzylidene)indan-1-one), paraformaldehyde and suitable amine in 1:1.2:1 mol ratios. Amine part was changed as N-methylpiperazine (1), N-phenylpiperazine (2), N-benzylpiperazine (3), 1-(2-methoxyphenyl)piperazine (4), 1-(3-methoxyphenyl)piperazine (5), 1-(2-fluorophenyl)piperazine (6), 1-(4-fluorophenyl)piperazine (7), and 1-(3-trifluoromethyl)phenyl piperazine (8). Compounds were evaluated in terms of cytotoxic/anticancer and CA inhibitory effects. According to the results obtained, the compounds 2 and 8 had the highest potency selectivity expression (PSE) values (60.6 and 19.2, respectively). On the other hand, the compounds 3 (Ki = 209.6 ± 70.2 pM) and 5 (Ki = 342.66 ± 63.72 pM) had the lowest Ki values in CA inhibition experiments towards hCA I and hCA II, respectively. In conclusion, the compounds 2 (with cytotoxic/anticancer activity), 3 (with hCA I inhibiting activity) and 5 (with hCA II inhibiting activity) can be leading compounds of the study for further designs and evaluations.

Keywords: Carbonic anhydrase; Cytotoxicity; Mannich bases; Phenol; Vanillin.