Structure-antimicrobial activity relationships of monoketone curcuminoids

Abstract

Recently, monoketone curcuminoids (MKCs), or 1,5-diarylpentadien-3-one derivatives, have been reported as promising compounds with respect to their antimicrobial activity against a panel of cariogenic bacteria, including S. mutans. 5 Although some preliminary structure-relationships have been previously proposed, the effect of some important structure features on the antimicrobial activity was not evidenced. In this paper, we report on the antimicrobial activity of three MKCs derivatives against cariogenic bacteria aiming to better understand the structure-antimicrobial relationships among these compounds. Materials and methods Synthesis of monoketone curcuminoids 1-2, 1a-1b Compounds 1 and 2 (Scheme 1) were obtained by aldol condensation in acidic conditions, as previously reported. 6 Briefly, a mixture of acetone (580mg, 10mmol) and vanilin (20mmol) for compound 1 or 4-hidroxy-benzaldehyde (20mmol) for 2 was slowly added to acetic acid (50mL) saturated with hydrogen chloride at 0 oC. The reaction mixture was stirred at room temperature for 24h. Next, the crude reaction mixture was poured into ice-cold water (200mL) and then extracted with ethyl acetate (3x30mL). After drying the organic portion over MgSO 4 , filtration, and solvent removal under reduced pressure, the resulting solid was purified using silica gel flash column chromatography using hexane: ethyl acetate 1:1 (v/v) (Figure 1). Compounds 1a and 1b were obtained from 1 by catalytic hydrogenation. In this procedure, compound 1 dissolved in HPLC grade ethyl acetate was added to a high-pressure 1 reactor together with Pd/C (10%) and kept at room temperature under stirring, H 2 atmosphere, and pressure of 100 psi for 18h. 7 Chemical structures of compounds 1, 1a, 1b, and 2a were confirmed on the basis of NMR, IR, and MS analyses. (1E,4E)-1,5-bis (4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one (1): Yield 21%, orange powder. IR (KBr pellet) of 1 (C 19 H 18 O 5). ν max /cm-1 : 3411 (νOH), 3005 (νCH), 1714 (νC=O), 1589 (νC=C), 1093 (νC-O). LRESI-MS (m/z, % relative intensity): 327 (100) [M+H] + .