ORIGINAL RESEARCH Synthesis and SAR investigation of natural phenylpropene- derived methoxylated cinnamaldehydes and their novel Schiff bases as potent antimicrobial and antioxidant agents Upendra K. Sharma • Swati Sood • Nandini Sharma • Praveen Rahi • Rakesh Kumar • Arun K. Sinha • Arvind Gulati Received: 9 August 2012 / Accepted: 9 January 2013 Ó Springer Science+Business Media New York 2013 Abstract A series of cinnamyl compounds were synthe- sized from abundantly available methoxylated phenylprop- enes and evaluated for their antimicrobial activity by the broth microdilution method against fourteen opportunistic bacterial and fungal human pathogens. Structure–activity relationship studies indicated that methylenedioxy cinna- maldehyde exhibited promising broad-spectrum activity against the tested microorganisms and hence was used as a lead structure to synthesize novel Schiff bases/heterocyclic compounds (23–33) under microwave irradiation. Out of these, thiazole-based Schiff bases have shown promising antibacterial activity against B. subtilis (26; MIC 0.12 mM), M. luteus (27; MIC 0.20 mM), and S. aureus (27; MIC 0.20 mM). Also, the compounds 23–33 were investigated for in vitro antioxidant activity using DPPH • assay where compound 28 showed a maximum of 80.71 % inhibition. Keywords Methoxylated phenylpropenes  Cinnamaldehydes  Antimicrobial activity  Antioxidant activity  Schiff bases  Structure–activity relationship  Microwave-assisted synthesis Introduction The rapid development of pathogen resistance to most of the known antibiotics has become a pressing problem worldwide. Hence, to combat the resistant strains, there is a vital need of developing lead scaffolds for the synthesis of antimicrobial agents (Walsh, 2003; Gold and Moellering, 1996; Cohen, 1992), the success of which relies crucially on the search for new chemical entities (NCEs). However, the random screening of compound libraries is generally not favorable with the pharmaceutical industry for eco- nomic reasons. Under these perspectives, the design of molecules by combining different pharmacophores in one structure, particularly of natural origin, may lead to NCEs with increased antimicrobial activity. The use of plant-based antimicrobials (Bourgaud et al., 2001; Benavente-Garcia et al., 2000; Manach et al., 2005) or their semi-synthetic derivatives has received renewed attention due to the concerns for potential harmful effects of many synthetic chemicals on human health, environment, and non-target organisms. In this context, phenylpropene- rich essential oils (Dixon and Paiva, 1995; Benzoukian, 1986) are valuable plant-derived raw materials for the syn- thesis/semi-synthesis of bioactive organic compounds. Several methoxylated phenylpropenes such as asarone (2,4,5-tri- methoxyphenyl-1-propene), anethole(4-methoxyphenyl-1-pro- pene), and isosafrole (3,4-methylenedioxyphenyl-1-propene) are found in a major proportion in the essential oils of Acorus calamus, Foeniculum vulgare, and Illicium religiosum, respectively (Harborne and Baxter, 1993). These phenyl- propenes have been used since antiquity to preserve and flavor the food and as medicinal agents (Gross et al., 2002). However, studies have revealed that the trans-isomers of methoxylated phenylpropenes (e.g., a-asarone) are safe (Hernandez et al., 1993) for human consumption, while Electronic supplementary material The online version of this article (doi:10.1007/s00044-013-0484-9) contains supplementary material, which is available to authorized users. U. K. Sharma  N. Sharma  R. Kumar  A. K. Sinha (&) Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Post Box 6, Palampur 176061, Himachal Pradesh, India e-mail: aksinha08@rediffmail.com S. Sood  P. Rahi  A. Gulati Plant Pathology and Microbiology Lab, Hill Area Tea Science Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India 123 Med Chem Res DOI 10.1007/s00044-013-0484-9 MEDICINAL CHEMISTRY RESEARCH