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-1 H -inden-1-one ( 1, 2, 4, 5, 8 ), 2-(3-((substituted)piperazin-1-yl)methyl)-4-hydroxy-5-methoxybenzylidene)-2,3-dihydro-1 H -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 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 ), 1-(3-trifluoromethyl)phenyl piperazine ( 8 ). Compounds were evaluated in terms of cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 2 and 8 showed 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. As a result, the compounds 2 (cytotoxic/anticancer), 3 (hCA I) and 5 (hCA II) can be lead compounds of the study for further designes and evaluations.