Synthesis of b-ionone derived chalcones as potent antimicrobial agents Vishal Sharma a , Gurpreet Singh a , Harpreet Kaur c , Ajit K. Saxena b , Mohan Paul S. Ishar a,⇑ a Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143 005, Punjab, India b Indian Institute of Integrative Medicine, Pharmacology Division, Jammu 180 001, J & K, India c Department of Microbiology, Guru Nanak Dev University, Amritsar-143 005, Punjab, India article info Article history: Received 29 May 2012 Revised 25 July 2012 Accepted 22 August 2012 Available online 30 August 2012 Keywords: b-Ionone b-Ionone derived chalcones Antibacterial activity Antifungal activity abstract A series of chalcones (3a–v) have been synthesized by condensation of b-ionone (1) with a variety of alde- hydes (2a–v). The synthesized compounds have been screened for their in vitro antimicrobial activity against five bacterial and five fungal strains, using disc diffusion assay. The evaluated compounds display a wide range of activities, from completely inactive to the highly active compounds. Some of the compounds are also active against methicillin resistant staphylococcus aureus (MRSA). Ó 2012 Elsevier Ltd. All rights reserved. Life threatening infections caused by pathogenic fungi and bacte- ria are becoming increasingly common and widespread epidemics in the world, especially in individuals with suppressed immune system that is, cancer, AIDS patients etc. Antimicrobial treatment used for these infections is also a serious public health threat because of rapid development of resistance by increasing number of pathogenic microorganisms against multiple drugs. 1–3 Therefore, efforts are directed towards the design, synthesis and evaluation of the new chemical therapeutics as alternative to existing antimicrobial ther- apy. Chalcones represent an important group of natural products. Both naturally occurring and synthetic chalcones (Fig. 1) exhibit remarkable pharmacological activities such as antioxidant, 4 tyrosi- nase inhibition, 5 antileishmanial, 6 anticancer, 7 antiangiogenic, 8 anti-inflammatory, 9 nitric oxide inhibition, 10 antifungal, 11 antibac- terial 12–15 etc. Recently, Liaras et al. have reported some thiazole based chalcones displaying greater activity than reference drugs. 12b Chalcones such as 4-hydroxychalcone and 2,4-dihydroxychalcone have been found to exhibit moderate activity against MRSA when used alone and showed significant synergistic effect in combination with non beta-lactam antibiotics. 12c On other hand, b-ionone is an important phytochemical present in many fruits, vegetables and grains and known to exert diverse biological activities including antibacterial and antifungal activ- ity. 16–18 Taking cognizance of wide range of biological activities of both b-ionone and chalcones, particularly antibacterial and antifungal, it was decided to synthesize some b-ionone derived chalcones so that synergistic effect of both valuable moieties in single scaffold may result in formation of some potential antimi- crobial molecules. Recently, some ionones based chalcones have been reported as potential anticancer agents against prostate can- cer cells. 7b b-ionones derived chalcones (3a–v) were prepared by condensing freshly distilled b-ionone (1, Scheme 1, Table 1) with distilled/crystallized subsituted benzaldehydes (2a–v) in the presence of 10% NaOH water-ethanol solution. 19 The products were purified through chromatography over silica gel (hexane, hexane-benzene gradient) and/or by crystal1ization with diethyl- ether and characterized through spectral data (IR, 1 H NMR, 13 C NMR, mass) and elemental analysis. The assigned structures of chalcones are based on detailed spec- troscopic analysis. IR spectrum of compound 3i revealed a strong band at 1650 cm À1 , along with resonance in its 13 C NMR at d 188.4 indicating the presence of a keto carbonyl function. Its 1 H NMR revealed, besides aromatic proton resonances in the region d 7.27–7.15, two b-protons of a,b-unsturated carbonyl moiety showed up as doublets at d 7.97 and 7.43 with trans olefinic-H cou- pling constant J = 15.9 Hz and two a-protons appeared as doublets at d 6.87 and 6.64 (J = 15.9 Hz). Antibacterial activity In vitro antibacterial studies of various compounds (3a–v) were carried out against Gram negative and gram positive bacterial strains by disk-diffusion assay. 20 The Gram positive strains used were Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 2451) and gram negative bacteria were Escherichia coli (MTCC 82), Pseudomonas aeruginosa (MTCC 2642), Salmonella typhimurium (MTCC 1251). The activity of compounds was determined in com- 0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bmcl.2012.08.084 ⇑ Corresponding author. Tel.: +91 183 2258802x3321; fax: +91 183 2258820. E-mail address: mpsishar@yahoo.com (M.P.S. Ishar). Bioorganic & Medicinal Chemistry Letters 22 (2012) 6343–6346 Contents lists available at SciVerse ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl