Indian Journal of Chemistry Vol. 54B, October 2015, pp 1235-1246 Antibacterial and antioxidant activity evaluation of novel symmetrical and unsymmetrical C5-curcuminoids Sunny Manohar a † , Anuj Thakur a , Rohit Bhatia b ‡ , Suresh Walia b , Prija Ponnan a & Diwan S Rawat* a a Department of Chemistry, University of Delhi, Delhi 110 007, India b Division of Agricultural Chemicals, Indian Agricultural Research Institute (IARI), New Delhi 110 012, India E-mail: dsrawat@chemistry.du.ac.in Received 24 November 2014; accepted (revised) 28 August 2015 Curcumin remains one of the most widely studied natural product due to its wide range of biological activities but because of the presence of central -diketone unit which is responsible for its poor bioavailability, this molecule cannot be developed as a drug. In order to overcome this, curcumin has been modified to metabolically stable symmetrical and unsymmetrical C5-curcuminoids and their in vitro antibacterial and antioxidant activity were studied. Few of the synthesized C5-curcuminoids (10, 11 and 25) displayed excellent potency (MIC value 1.5 to 6.25 μg/mL) against the tested bacterial strains. Six of the analogues (10, 12-15 and 25) were also found to exhibit good antioxidant activity (IC 50 values 33.87 to 49.45 μg/mL) in a DPPH free radical scavenging assay. The test compounds have been further subjected to in silico ADMET analysis and various pharmacokinetic properties were calculated. Compounds 20, 23-25 are predicted to have less toxic effects and follow the permissible pharmacokinetic criterion. Keywords: Curcumin, C5-curcuminoids, antibacterial, antioxidant Curcumin (Figure 1a), a principle constituent of the perennial herb Curcuma longa, is well known for its medicinal potential since 1900 BC. Its use in liver injury, arthritis, cataract formation, cardiovascular diseases, Alzheimer, diabetes and wound healing has been well documented in Indian Ayurveda 1,2 . Due to its ability to interact with multiple molecular signaling pathways involved in carcinogenesis, it has been the subject of intense pharmacological studies globally in both industry and academia 3-5 . Curcumin is also known to exhibit potent antibacterial activity against both gram-negative and gram-positive bacteria including several multi-drug resistant bacterial strains 6-11 . In addition, being a free radical scavenger, it was found to be an effective antioxidant in different in vitro assays including DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] and DMPD (N,N-dimethyl-p-phenylenediamine dihydrochloride) radical scavenging, hydrogen peroxide scavenging and metal chelating activities 12 . The anti- oxidant properties of curcumin plays a significant role in inhibiting peroxidation of membrane lipids and oxidative damage of DNA and proteins associated with various pathological conditions such as atherosclerosis and neurodegenerative diseases 13 . Curcumin’s excellent medicinal potency was attri- buted to its safe toxicity profile and in a phase I clinical trial it was demonstrated that curcumin is safe and non-toxic even at high oral doses of 12 g/day 14 . In spite of these brilliant pharmaceutical properties, curcumin suffers from several disadvantages like poor systemic bioavailability, rapid metabolism and low solubility which in turn reduces its capability of becoming a potential drug candidate 15 . The presence of central -diketone functionality in curcumin was found to be the main culprit behind these observations, which is a substrate for liver aldoketo reductases and hence may contribute for the rapid metabolism of curcumin in vivo 16 . However, modification of central -diketone moiety of curcumin to mono-keto group leads to the development of C5-curcuminoids having 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore. The C5-curcuminoids have shown better pharmacological profile like superior bioavailability, high potency and improved metabolic stability when compared with curcumin and other C7-curcuminoids 17-22 . Encouraged by the safety profile and potent activity of C5-curcuminoids, we recently reported cytotoxic potential of some symmetrical C5-curuminoids 17,23,24 . In continu- _________ † Current Address: Department of Chemistry, Deen Dayal Upadhyaya College (University of Delhi), Shivaji Marg, Karampura, New Delhi 110 015, India ‡ Current Address: Division of Sustainable Chemistry, Peoples Action for Livelihood & Sustainability (PALS), New Delhi 110 092, India