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Synthesis and biological evaluation of novel curcumin analogues as anti-inflammatory, anti-cancer and anti-oxidant agents

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Abstract

A series of novel curcumin analogues 5a–m were synthesized by Claisen-Schmidt condensation of various aromatic and heteroaromatic amides of 3-aminoactophenones 4a–m with 3-bromo-2,4,6-trimethoxybenzaldehyde and characterized by IR, 1H NMR and mass spectroscopic analysis and were evaluated for anti-inflammatory, anti-cancer and anti-oxidant activity. Out of the 13 synthesized compounds, compounds 5f, 5j and 5m were excellent inhibitors of TNF-α and IL-6. Compounds 5c, 5e, 5b and 5d showed potent COX-2 inhibition, compounds 5d and 5f have shown good trypsin inhibition and compounds 5e, 5g and 5c exhibited excellent β-glucuronidase inhibition. Compounds 5l and 5m showed potent anti-cancer activity against selected five human cancer cell lines. All the compounds exhibited moderate free radical scavenging activity, while compounds 5a and 5m were excellent OH radical scavengers.

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References

  • Ahn CM, Shin W-S, Woo HB, Lee S, Lee H-W (2004) Synthesis of symmetrical bis-alkynyl or alkyl pyridine and thiophene derivatives and their antiangiogenic activities. Bioorg Med Chem Lett 14:3893–3896

    Article  PubMed  CAS  Google Scholar 

  • Ammon HP, Wahl MA (1991) Pharmacology of curcuma longa. Planta Med 57:1–7

    Article  PubMed  CAS  Google Scholar 

  • Bandgar BP, Patil SA, Gacche RN, Korbad BL, Hote BS, Kinkar SN, Jalde SS (2010) Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett 20:730–733

    Article  PubMed  CAS  Google Scholar 

  • Bartolome B, Nunez V, Monagas M, Gomez-Cordoves C (2004) In vitro antioxidant activity of red grape skins. Eur Food Res Technol 218:173–177

    Article  CAS  Google Scholar 

  • Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundey GR (1986) Stimulation of bone-resorption and inhibition of bone formation in vitro by human tumor necrosis factors. Nature 319:516–518

    Article  PubMed  CAS  Google Scholar 

  • Bilfinger TV, George BS (2002) The role of protease inhibition with emphasis on the effects of inflammation and vascular immune phenomena. Curr Pharm Des 8:125–133

    Article  Google Scholar 

  • Cooper TH, Clark JG, Guzinski JA (1994) In: Ho C-T (ed) Food phytochemicals for cancer prevention II: ACS symposium series. American Chemical Society, New York, pp 231–236

  • Dengler WA, Schulte J, Berger DP, Mertelsmann R, Fiebig HH (1995) Development of a propidium iodide fluorescence assay for proliferation and cytotoxicity assays. Anticancer Drugs 6:522–532

    Article  PubMed  CAS  Google Scholar 

  • Dominic SCR (2009) Seminars in arthritis and rheumatism, vol 38. Elsevier, Amsterdam, pp 382–386

    Google Scholar 

  • Elliott MJ, Maini RN (1994) New directions for biological therapy in rheumatoid arthritis. Int Arch Allergy Immunol 104:112–125

    Article  PubMed  CAS  Google Scholar 

  • Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Ann Rev Immunol 14:397–440

    Article  CAS  Google Scholar 

  • Gacche RN, Dhole NA (2006) Antioxidant and possible anti-inflammatory potential of selected medicinal plants prescribed in the Indian traditional system of medicine. Pharm Biol 44:389–395

    Article  CAS  Google Scholar 

  • Geronikaki AA, Gavalas AM (2006) Antioxidants and inflammatory disease: synthetic and natural antioxidants with anti-inflammatory activity. Comb Chem High Throughput Screen 9:425–442

    Article  PubMed  CAS  Google Scholar 

  • Goldfeld AE, Strominger JL, Doyle C (1991) Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines. J Exp Med 174:73–81

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    PubMed  CAS  Google Scholar 

  • Hotamisligil G, Arner P, Caro J, Atkinson R, Spiegelman B (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415

    Article  PubMed  CAS  Google Scholar 

  • Hsu CH, Cheng AL (2007) Clinical studies with curcumin. Adv Exp Med Biol 595:471–480

    Article  PubMed  Google Scholar 

  • Huang MT, Smart RC, Wong CQ, Conney AH (1988) Inhibitory effect of curcumin, chlorogenic acid, caffeic acid and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 48:5941–5946

    PubMed  CAS  Google Scholar 

  • Huang MT, Newmark HL, Frenkel KJ (1997) Inhibitory effects of curcumin on tumorigenesis in mice. Cell Biochem Suppl 27:26–34

    Article  CAS  Google Scholar 

  • Hwang C, Catanaga M, Gale A, Gatanaga T (1993) Mechanism of release of soluble forms of tumor necrosis factor/lymphotoxin receptors by phorbol myristate acetate-stimulated human THP-1 cells in vitro. J Immunol 151:5631–5638

    PubMed  CAS  Google Scholar 

  • Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 59:597–601

    PubMed  CAS  Google Scholar 

  • Lovering F, Zhang Y (2005) Therapeutic potential of TACE inhibitors in stroke. Curr Drug Tar 4:161–168

    CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall R (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Mehta K, Pantazis P, McQueen T, Aggarwal BB (1997) Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs 8:470–481

    Article  PubMed  CAS  Google Scholar 

  • Moreland LW, LWJr Heck, Koopam WJ (1997) Biological agents for treating rheumatoid arthritis. Arthritis Rheum 40:397–409

    Article  PubMed  CAS  Google Scholar 

  • Nadkarni KM (ed) (1976) In: India materia medica. Popular Prakashan Publishing Co, Bombay, pp 414–416

  • Nash T (1953) The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 55:416–421

    PubMed  CAS  Google Scholar 

  • Newton RC, Decicco C (1999) Therapeutic potential and strategies for inhibiting tumor necrosis factor-alpha. J Med Chem 42:2295–2314

    Article  PubMed  CAS  Google Scholar 

  • Odeh M (1997) New insinghts into the pathogenesis and treatment of rheumatoid arthritis. Clin Immunpathol 83:103–116

    Article  CAS  Google Scholar 

  • Oppenheim JJ, Feldmann M (eds) (2001) Introduction to the role of cytokines in inate host defense and adaptive immunity. In: Cytokine reference, vol 1. Academic Press, New York, NY, pp 3–20

  • Pan M-H, Huang T-M, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27:486–494

    PubMed  CAS  Google Scholar 

  • Papadakis KA, Targan SR (2000) Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 51:289–298

    Article  PubMed  CAS  Google Scholar 

  • Robinson TP, Hubbard RBIV, Ehlers TJ, Arbiser JL, Goldsmith DJ, Bowen JP (2005) Synthesis and biological evaluation of aromatic enones related to curcumin. Bioorg Med Chem 13:4007–4013

    Article  PubMed  CAS  Google Scholar 

  • Rus H, Niculescu F, Vlaicu R (1991) Tumor necrosis factor-alpha in human arterial wall with atherosclerosis. Atherosclerosis 89:247–254

    Article  PubMed  CAS  Google Scholar 

  • Sakalatvala J (1986) Tumour necrosis factor-α stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 322:547–549

    Article  Google Scholar 

  • Sasaki K, Matsumato I, Beppu M (1991) Affinity chromatography. Tokyo Kagaku Dojin, Tokyo, pp 117–130

    Google Scholar 

  • Selmaj K, Raine C, Cannella B, Bronson C (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949–954

    Article  PubMed  CAS  Google Scholar 

  • Sharma RA, Steward WP, Gescher AJ (2007) Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 595:453–470

    Article  PubMed  Google Scholar 

  • Tandon M, Tandon P, Barthwal JP, Bhalla TN, Bhargava KP (1982) Anti- inflammatory and antiproteolytic activities of newer indolyl isoquinolines. Drug Res 32:1233–1235

    CAS  Google Scholar 

  • Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117:244–279

    Article  PubMed  CAS  Google Scholar 

  • Tracy KJ, Cerami A (1994) Tumor necrosis factor: a pleiotropic cytokine and therapuetic target. Ann Rev Med 45:491–503

    Article  Google Scholar 

  • Woo HB, Shin W-S, Lee S, Ahn CM (2005) Synthesis of novel curcumin mimics with asymmetrical units and their anti-angiogenic activity. Bioorg Med Chem Lett 15:3782–3786

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

BSH is thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi for the award of SRF, as well as to Mr. Mahesh Nambiar and Mrs. Asha Almeida, Piramal Life Sciences Ltd., Mumbai for screening of the compounds against TNF-α. IL-6 and human cancer lines.

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Authors and Affiliations

  1. Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur, 413 255, India

    Babasaheb P. Bandgar

  2. Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded, 431 606, India

    Babasaheb P. Bandgar, Baliram S. Hote & Shivkumar S. Jalde

  3. School of Life Sciences, Swami Ramanand Teerth Marathawada University, Nanded, 431 606, India

    Rajesh N. Gacche

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  1. Babasaheb P. Bandgar
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  2. Baliram S. Hote
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  3. Shivkumar S. Jalde
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  4. Rajesh N. Gacche
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Correspondence to Babasaheb P. Bandgar.

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Bandgar, B.P., Hote, B.S., Jalde, S.S. et al. Synthesis and biological evaluation of novel curcumin analogues as anti-inflammatory, anti-cancer and anti-oxidant agents. Med Chem Res 21, 3006–3014 (2012). https://doi.org/10.1007/s00044-011-9834-7

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  • DOI: https://doi.org/10.1007/s00044-011-9834-7

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