DOCKING, SYNTHESIS, CHARACTERIZATION AND ANTICANCER ACTIVITY OF 4-(4’-HYDROXY, 3’-METHOXY) PHENYL, BUT-2-ONE-3-ENE, A CURCUMIN ANALOGUE PRECURSOR

  • Karpakavalli M. Karpagam College of Pharmacy, Coimbatore 641032, Tamilnadu, India
  • Preethi Kumar JSS College of Pharmacy, Ooty 643001, Tamilnadu, India
  • Sanglimuthu A. Karpagam University, Coimbatore 641021 Tamilnadu, India
  • Kumar E. P. Nehru College of Pharmacy, Thrissur 680001, Kerla, India

Abstract

Objective: Curcumin, a phytoconstituent of Curcuma longa has pursued the attention of research chemists, as it is found to possess a number of pharmacological activities. Autodock is an automated procedure for predicting the interaction of ligands with biomacromolecular targets. 4-(4’-hydroxy, 3’-methoxy) phenyl, but-2-one-3-ene, a curcumin analog precursor is aimed to be synthesized and tested for anticancer activity.

Methods: Autodock software utilized for the prediction of the fruitfulness of the target molecule. The aldol reaction is a powerful means of forming carbon–carbon bonds in organic chemistry. Aldol condensation of monocarbocyclic aldehyde and the enol form of a 2, 4-diketone in the presence of an organic amine catalyst, the principle is used for the synthesis of said molecule. The invention also relates to the use of the synthesized product for in vivo acute toxicity and in vitro anticancer activity.

Results: The synthesized compound was characterized both by physical and spectral data. In acute toxicity study, no mortality and thereby no toxic effect from the compound (500-62.5 µg/ml). Against MCF-7, the test drug exhibited potent cytotoxicity with CTC50 values ranging from 42.0 to 89.0 when tested with drug concentrations ranging from 500-62.5 µg/ml and average CTC50 was 125 µg/ml while with Vero cell line the compound showed mild cytotoxicity.

Conclusion: The experiments confirmed the fact of reliability of the synthesized compound 4-(4’-hydroxy, 3’-methoxy) phenyl, but-2-one-3-ene, a curcumin analog precursor for anti-cancer activity.
Keywords: Curcumin analogue, Docking, Synthesis, Characterization, Acute toxicity, Anti-cancer activity

References

1. Bala K. NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal models. Ann N Y Acad Sci 2006;1035:68-84.
2. Khurana S, Jain S, Banerjee BD, Sharma KK. Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats. Human Exp Toxicol 2012;31:686-97.
3. Kiran B, Tripathy B, Sharma S, Deepak A. Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology 2006;7:81-9.
4. Syu Wan. Involvement of the. beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem Pharmacol 1998;52:519-25.
5. Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A. Curcumin, demethoxy curcumin, bisdemethoxycurcumin, tetrahydro-curcumin, and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through an ROS-n dependent mechanism. Carcinogens 2007;28:1765-73.
6. Agrawal DK, Mishra PK. Curcumin and its analogues: potential anticancer agents. Res Rev 2010;30:818-60.
7. Thaloor D, Singh AK, Sidhu GS, Prasad PV, Kleinman HK. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell Growth Differ 1998;9:305-12.
8. Van Erk M, Teuling E, Staal Y, Huybers S, Van Bladeren P. Time and dose-dependent effects of curcumin on gene expression in human colon cancer cells. J Carcinogene 2004;3:8.
9. Holy JM. Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells. Mutat Res/Gene Toxicol Environ Mutagene 2002;518:71-84.
10. Fusheng Yang. Curcumin inhibits the formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005;280:5892-901.
11. Parveen I. Synthesis and anticancer activity of nordihydroguaiaretic acid (NDGA) and analogues. Anti-Cancer Drug Design 2000;16:261-70.
12. Artiser JL. Synthesis of dibenzoyl methane derivatives and inhibition of mutagenicity in salmonella typhimurium. Chem Abstract 1998;117:480-6.
13. Ruby AJ. Antitumor-promoting effects of cyclic diarylheptanoids on epstein-barr virus activation and two-stage mouse skin carcinogenesis. Canc Lett 1995;15:135-40.
14. Gautam SC. Cytotoxicity of curcuminoids and some novel compounds from curcuma zedoary. J Nat Prod 2007;61:1531-4.
15. Schneider G, Heinz K. Molecular design, concepts and applications. John Wiley and Sons; 2008.
16. Schames JR. Discovery of a novel binding trench in HIV integrase. J Med Chem 2004;47:1879-81.
17. Nurfina AN. Synthesis of naturally occurring curcuminoids and related compounds. Chem Abstract 1997;103:1780-92.
18. Rouset Y. Synthesis and 1HNMR-spectroscopic investigations of new curcumin analogs. J Prakt Chem 1973;334:656-700.
19. Pedersen F. Direct synthesis of demethoxy curcumin. CR. Acad Sci Paris: Ser II; 1985. p. 479-82.
20. Barry MT. Direct asymmetric Zn-aldol reaction of methyl vinyl ketone and its synthetic applications. J Am Chem Soc 2005;127:8602–3.
21. Christophe A. (Diisopinocampheyl)borane-mediated reductive aldol reactions of acrylate esters: enantioselective synthesis of anti-aldols. Org Lett 2013;15:3922–5.
22. Manabe K. Synthetic reactions using organometallics in water. Aldol and allylation reactions catalyzed by Lewis acid-surfactant-combined catalysts/Bronsted acids systems. Inorg Chim Acta 1999;26:158-63.
23. Argiles JM, Azcon-Bieto J. The metabolic environment of cancer. Mol Cell Biochem 1988;81:3-17.
24. Rudden RW. Cancer biology. 4th edition. Oxford University Press; 2007. p. 9-20.
25. Reynolds RJ, Schecker JA. Radiation cell cycle and cancer. Loss Almos Sci 1995;23:74-6.
26. Philip S, Rista S, Dominic S, Anne M, James M. New colorimetric cytotoxic assayfor anti cancer drug screening. J Natl Cancer Inst 1990;82:1107-12.
Statistics
336 Views | 1716 Downloads
How to Cite
M., K., P. Kumar, S. A., and K. E. P. “DOCKING, SYNTHESIS, CHARACTERIZATION AND ANTICANCER ACTIVITY OF 4-(4’-HYDROXY, 3’-METHOXY) PHENYL, BUT-2-ONE-3-ENE, A CURCUMIN ANALOGUE PRECURSOR”. International Journal of Current Pharmaceutical Research, Vol. 8, no. 4, Oct. 2016, pp. 1-5, doi:10.22159/ijcpr.2016v8i4.15266.
Section
Original Article(s)