Submit Manuscript | http://medcraveonline.com Abbreviations: MKCs, monoketone curcuminoids Introduction Dental caries constitutes a major public health concern worldwide. This pathology is caused by acidogenic and aciduric bacteria, which produce a structurally and functionally organized bioflm (dental plaque)on the tooth surface. 1 Streptococcus mutans is one of the most important colony-forming bacteria present in the bucal microbiota, stands out due its ability of producing substances that favor adhesion and the accumulation of other microorganisms, forming a resistant extracellular matrix that can destroy dental hard tissue. 2 Brushing and fossing the teeth to remove dental plaque, as well as conducting periodic dental cleaning or prophylaxis are the most effcient ways to prevent caries. However, most people fail to maintain an effcient bioflm control through mechanical removal only, which has increased the use of oral products containing antimicrobial agents to diminish bioflm formation on the tooth surface. 3 Although chlorhexidine is currently the most effective anti plaque agent, its use have been recommended by dentists only for short periods due to reversible local side effects. 4 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 Briefy, 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 , fltration, and solvent removal under reduced pressure, the resulting solid was purifed using silica gel fash 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 confrmed 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] + . NMR 1 H (400MHz, CDCl 3 ): δ 3.95 (6 H, s, H10=H10’), 6.93 (2 H, d, J 2,3=2’,3’ =15.8Hz, H2=H2’), 6.94 (2 H, d, J 6,5=6’,5’ =8.2Hz, H6=H6’), 7.11 (2 H, d, J 9,5=9’,5’ =1.4Hz, H9=H9’), 7.17 (2 H, dd, J 5,6=5’,6’ =8.2, J 5,9=5’,9’ =1.4Hz, H5=H5’), 7.67 (2 H, d, J 3,2=3’,2’ =15.8Hz, H3=H3’), 7.67 (2 H, d, J 3,2=3’,2’ =15.8Hz, H3=H3’). 13 C (100MHz, CDCl 3 ): δ 56.2 Int J Complement Alt Med. 2018;11(6):347‒350. 347 © 2018 Vieira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Structure-antimicrobial activity relationships of monoketone curcuminoids Volume 11 Issue 6 - 2018 Tatiana M Vieira, 1 Maria ALV Ambrosio, 2 Carlos HG Martins, 2 Antônio EM Crotti 1 1 Departamento de Química, Faculdade de Filosofa, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Brazil 2 Laboratorio de Pesquisa em Microbiologia Aplicada, Universidade de Franca, Brazil Correspondence: Antônio EM Crotti, Departamento de Química, Faculdade de Filosofa, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, Monte Alegre, CEP 14040-901 Ribeirão Preto, SP, Brazil, Tel +55 16 3515 3747, Fax 55 16 3515 4838, Email Received: October 22, 2018 | Published: November 15, 2018 Abstract Background: Dental caries is a major public health concern worldwide. In this paper, we investigated the antimicrobial activity of three synthetic monoketone curcuminoids (MKCs) against a representative panel of cariogenic bacteria and examined some structure-antimicrobial activity relationships of MKCs. Methods: MKCs 1 (curcumin A) and 2 were obtained by Claisen-Schmidt condensation in acidic conditions. Compounds 1a and 2a were obtained from 1 by catalytic hydrogenation. The minimum inhibitory concentration (MIC) values of 1a, 1b, and 2 were determined by using the broth micro dilution method in 96-well microplates. Chlorhexidine was used as positive control. Results: Compound 2 afforded the lowest MIC values against Streptococcus mutans (MIC=50μg/mL) and Streptococcus mitis (MIC=50μg/mL), as well as moderate activity against S. sanguinis (MIC=100μg/mL), S. salivarus (MIC=200μg/mL). These results revealed that the antimicrobial activity of MKCs is enhaced by the presence of a hydroxy group at the aromatic rings, as well as the carbonyl group at C1 and the double bonds between C2-C3 and C2’-C3’. Conclusion: Compounds 1 and 2 displays promising antimicrobial activity against some cariogenic bacteria. Our results suggest that these compounds might be promising for the development of new oral care products. Keywords: antibacterial activity, dental caries, monoketone curcuminoids, oral pathogens, Streptococcus mutans International Journal of Complementary & Alternative Medicine Research Article Open Access