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Medicinal Chemistry Research

, Volume 25, Issue 6, pp 1175–1192 | Cite as

Ferulic acid amide derivatives as anticancer and antioxidant agents: synthesis, thermal, biological and computational studies

  • Naresh KumarEmail author
  • Sandeep Kumar
  • Sheenu Abbat
  • Kumar Nikhil
  • Sham M. Sondhi
  • Prasad V. Bharatam
  • Partha Roy
  • Vikas Pruthi
Original Research

Abstract

The design and microwave-assisted synthesis of four series (IIIa–IIIo, Va–Vg, VIIa–VIIg and IXa–IXe) of mono and bis-amide derivatives of ferulic acid have been achieved under solvent-free conditions and, subsequently characterized by spectroscopic techniques. During thermal analysis, all the compounds were found stable up to 100 °C and decomposed through single step at higher temperature. The derivatives were screened for their in vitro cytotoxicity and antioxidant activity, respectively and observed that compound Vb was most active against breast (MCF-7; IC50 = 07.49 µM and MDA-MB-231; IC50 = 07.28 µM), Vd against lung (A549; IC50 = 07.11 µM) and liver (HepG2; IC50 = 08.32 µM), and Ve against cervical (HeLa; IC50 = 07.14 µM) cancer cell lines, while compounds IIIf, IIIl, IIIo, VIIe and IXa–IXe were found to exhibit the strong antioxidant activity with respect to their parent molecule. Previous reports for the biological applications of ferulic acid amides also confirmed the importance of work presented here. The 3D-QSAR studies for anticancer and antioxidant activities were also performed by using CoMFA, and the corresponding contour maps of electrostatic and steric fields have been computed. Statistical analysis between experimental and CoMFA-predicted data for pIC50 have been accomplished by curve fitting analysis which showed the significant correlation.

Graphical Abstract

Keywords

Ferulic acid Amide derivatives Anticancer and antioxidant activity 3D-QSAR CoMFA 

Notes

Acknowledgments

Naresh Kumar gratefully acknowledges CSIR, New Delhi, India, for financial assistance, Indian Institute of Technology Roorkee and NIPER Mohali for instrumentation facility.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.

Supplementary material

44_2016_1562_MOESM1_ESM.docx (15.8 mb)
Supplementary material 1 (DOCX 16186 kb)

References

  1. Basoglu S, Yolal M, Demirci S, Demirbas N, Bektas H, Karaoglu SA (2013) Design, synthesis and antimicrobial activities of some azole derivatives. Acta Pol Pharm 70(2):229–236PubMedGoogle Scholar
  2. Blois MS (1958) Antioxidant determinations by the use of a stable free radical. Nature 181:1199–1200CrossRefGoogle Scholar
  3. Chung SY, Champagne ET (2011) Ferulic acid enhances IgE binding to peanut allergens in Western blots. Food Chem 124(4):1639–1642CrossRefGoogle Scholar
  4. Clifford MN (1990) Chlorogenic acids and other cinnamates–nature, occurrence and dietary burden. J Sci Food Agric 79(3):362–372CrossRefGoogle Scholar
  5. Cramer RD, Bunce JD, Patterson DE, Frank IE (1988a) Cross-validation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant Struct Act Relat 7(1):18–25CrossRefGoogle Scholar
  6. Cramer RD, Patterson DE, Bunce JD (1988b) Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110(18):5959–5967CrossRefPubMedGoogle Scholar
  7. Ferhat M, Ghorab H, Laggoune S, Ghannadi A, Sajjadi SE, Touzani R, Kabouche A, Kabouche Z (2014) Composition and antioxidant activity of the essential oil of Thymus dreatensis from Algeria. Chem Nat Comp 50(4):747–749CrossRefGoogle Scholar
  8. Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity-a rapid access to atomic charges. Tetrahed 36(22):3219–3228CrossRefGoogle Scholar
  9. Goel N, Kumar N (2014) Study of supramolecular frameworks having aliphatic dicarboxylic acids, N, N′-bis(salicyl)ethylenediamine and N, N′-bis(salicyl)butylenediamine. J Mol Struct 1071:60–70CrossRefGoogle Scholar
  10. Goel N, Singh UP (2013) Syntheses, structural, computational and thermal analysis of acid-base complexes of picric acid with N-heterocyclic bases. J Phys Chem A 117(40):10428–10437CrossRefPubMedGoogle Scholar
  11. Herrmann K (1989) Occurrence and content of hydroxycinnamic and hydroxybenzoic acid compounds in foods. Crit Rev Food Sci Nutr 28(4):315–347CrossRefPubMedGoogle Scholar
  12. Hosoda A, Ozaki Y, Kashiwada A, Mutoh M, Wakabayashi K, Mizuno K, Nomura E, Taniguchi H (2002) Syntheses of ferulic acid derivatives and their suppressive effects on cyclooxygenase-2 promoter activity. Bioorg Med Chem 10(4):1189–1196CrossRefPubMedGoogle Scholar
  13. Huang GY, Cui C, Wang ZP, Li YQ, Xiong LX, Wang LZ, Yu SJ, Li ZM, Zhao WG (2013) Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity. Chem Cent J 7(33):1–12CrossRefGoogle Scholar
  14. Kiran T, Alekhya C, Lokesh B, Latha A, Prasad Y, Mounika T (2015) Synthesis, characterization and biological screening of ferulic acid derivatives. J Can Ther 6:917–931CrossRefGoogle Scholar
  15. Kumar N, Bhalla TC (2011) In silico analysis of amino acid sequences in relation to specificity and physiochemical properties of some aliphatic amidases and kynurenine formamidases. J Bioinform Seq Anal 3(6):116–123Google Scholar
  16. Kumar N, Garg A (2014) Structural optimization and docking studies of anatoxin-a: a potent neurotoxin. Afr J Biotechnol 13(30):3092–3100CrossRefGoogle Scholar
  17. Kumar N, Pruthi V (2014) Potential applications of ferulic acid from natural sources. Biotechnol Rep 4:86–93CrossRefGoogle Scholar
  18. Kumar N, Pruthi V (2015) Structural elucidation and molecular docking of ferulic acid from Parthenium hysterophorus possessing COX-2 inhibition activity. 3. Biotech 5(4):541–551Google Scholar
  19. Kumar S, Kumar N, Roy P, Sondhi SM (2014) Efficient synthesis of heterocyclic compounds derived from 2,6-dioxopiperazine derivatives and their evaluation for anti-inflammatory and anticancer activities. Med Chem Res 23(9):3953–3969CrossRefGoogle Scholar
  20. Kumar N, Pruthi V, Goel N (2015) Structural, thermal and quantum chemical studies of p-coumaric and caffeic acids. J Mol Struct 1085:242–248CrossRefGoogle Scholar
  21. Lever SD, Papadaki M (2004) Study of condition-dependent decomposition reactions: part I. The thermal behaviour and decomposition of 2-nitrobenzoyl chloride. J Hazard Mater 115(1–3):91–100CrossRefPubMedGoogle Scholar
  22. Li W, Li N, Tang Y, Li B, Liu L, Zhang X, Fu H, Duan JA (2012a) Biological activity evaluation and structure–activity relationships analysis of ferulic acid and caffeic acid derivatives for anticancer. Bioorg Med Chem Lett 22(19):6085–6088CrossRefPubMedGoogle Scholar
  23. Li WJ, Cheng XL, Liu J, Lin RC, Wang GL, Du SS, Liu ZL (2012b) Phenolic Compounds and Antioxidant Activities of Liriope muscari. Molecules 17(2):1797–1808CrossRefPubMedGoogle Scholar
  24. Middleton E Jr, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52(4):673–751PubMedGoogle Scholar
  25. Mori H, Kawabata K, Yoshimi N, Tanaka T, Murakami T, Okada T, Murai H (1999) Chemopreventive effects of ferulic acid on oral and rice germ on large bowel carcinogenesis. Anticancer Res 19(5A):3775–3783PubMedGoogle Scholar
  26. Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T (2013) Ferulic acid Is a nutraceutical β-secretase modulator that improves behavioral impairment and Alzheimer-like pathology in transgenic mice. PLoS One 8:1–15Google Scholar
  27. Narang AS, Desai DS, Lu YRI (eds) (2009) Pharmaceutical perspectives of cancer therapeutics. Springer. doi: 10.1007/978-1-4419-0131-6_2
  28. Ou S, Kwok KC (2004) Ferulic acid: pharmaceutical functions, preparation and applications in foods. J Sci Food Agric 84(11):1261–1269CrossRefGoogle Scholar
  29. Paiva LB, Goldbeck R, Santos WD, Squina FM (2013) Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field. Braz J Pharm Sci 49(3):395–411CrossRefGoogle Scholar
  30. Parkesh R, Childs-Disney JL, Nakamori M, Kumar A, Wang E, Wang T, Hoskins J, Tran T, Housman D, Thornton CA, Disney MD (2012) Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching. J Am Chem Soc 134(10):4731–4742CrossRefPubMedPubMedCentralGoogle Scholar
  31. Piazzon A, Vrhovsek U, Masuero D, Mattivi F, Mandoj F, Nardini M (2012) Antioxidant activity of phenolic acids and their metabolites: synthesis and antioxidant properties of the sulphate derivatives of ferulic and caffeic acids and of the acyl glucuronide of ferulic acid. J Agric Food Chem 60(50):12312–12323CrossRefPubMedGoogle Scholar
  32. Rosazza JPN, Huang Z, Dostal L, Volm T, Rousseau B (1995) Review: biocatalytic transformations of ferulic acid: an abundant aromatic natural product. J Ind Microbiol 15(6):457–471CrossRefPubMedGoogle Scholar
  33. Sajjadi SE, Naderi GH, Ziaii R, Zolfaghari B (2004) The antioxidant activity of polyphenolic fraction of Thymus daenensis Celak. Iran J Pharm Res 3(2):80–81Google Scholar
  34. Shamsipur M, Pourmortazavi SM, Beigi AKM, Heydari R, Khatibi M (2013) Thermal stability and decomposition kinetic studies of acyclovir and zidovudine drug compounds. AAPS Pharm Sci Tech 14(1):287–293CrossRefGoogle Scholar
  35. Shang YJ, Jin XL, Shang XL, Tang JJ, Liu GY, Dai F, Qian YP, Fan GJ, Liu Q, Zhou B (2010) Antioxidant capacity of curcumin-directed analogues: structure-activity relationship and influence of microenvironment. Food Chem 119:1435–1442CrossRefGoogle Scholar
  36. Sharma OP, Bhat TK (2009) DPPH antioxidant assay revisited. Food Chem 113(4):1202–1205CrossRefGoogle Scholar
  37. Sondhi SM, Kumar S, Kumar N, Roy P (2012) Synthesis anti-inflammatory and anticancer activity evaluation of some pyrazole and oxadiazole derivatives. Med Chem Res 21(10):3043–3052CrossRefGoogle Scholar
  38. Sultana R (2012) Ferulic acid ethyl ester as a potential therapy in neurodegenerative disorders. Biochim Biophys Acta 1822(5):748–752CrossRefPubMedGoogle Scholar
  39. Tamm LK, Abildgaard F, Arora A, Blad H, Bushweller JH (2003) Structure, dynamics and function of the outer membrane protein A (OmpA) and influenza hemagglutinin fusion domain in detergent micelles by solution NMR. FEBS Lett 555(1):139–143CrossRefPubMedGoogle Scholar
  40. Tan Z, Shahidi F (2011) Chemoenzymatic synthesis of phytosteryl ferulates and evaluation of their antioxidant activity. J Agric Food Chem 59(23):12375–12383CrossRefPubMedGoogle Scholar
  41. Teresa LS, Filipa SC, Maria PMM, Rita C, Tiago S, Jorge G, Nuno M, Fernanda B, Fernanda R, Elisiário TS, Jon H, Paulo JO (2011) Lipophilic caffeic and ferulic acid derivatives presenting cytotoxicity against human breast cancer cells. Chem Res Toxicol 24(5):763–774CrossRefGoogle Scholar
  42. Toshihiro A, Ken Y, Miho Y, Motohiko U, Yumiko K, Naoto S, Koichi A (2000) Triterpene alcohol and sterol ferulates from rice bran and their anti-inflammatory effects. J Agric Food Chem 48(6):2313–2319CrossRefGoogle Scholar
  43. Vashisth P, Kumar N, Sharma M, Pruthi V (2015) Biomedical applications of ferulic acid encapsulated electrospun nanofibers. Biotechnol Rep 8:36–44CrossRefGoogle Scholar
  44. Wang F, Lu W, Zhang T, Dong J, Gao H, Li P, Wang S, Zhang J (2013) Development of novel ferulic acid derivatives as potent histone deacetylase inhibitors. Bioorg Med Chem 21(22):6973–6980CrossRefPubMedGoogle Scholar
  45. Wiegand C, Heinze T, Hipler UC (2009) Comparative in vitro study on cytotoxicity, antimicrobial activity, and binding capacity for pathophysiological factors in chronic wounds of alginate and silver-containing alginate. Wound Repair Regen 17(4):511–521CrossRefPubMedGoogle Scholar
  46. Wold S (1991) Validation of QSAR’s. Quant Struct Act Relat 10:191–193CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Naresh Kumar
    • 1
    Email author
  • Sandeep Kumar
    • 2
  • Sheenu Abbat
    • 3
  • Kumar Nikhil
    • 1
  • Sham M. Sondhi
    • 2
  • Prasad V. Bharatam
    • 4
  • Partha Roy
    • 1
  • Vikas Pruthi
    • 1
  1. 1.Department of BiotechnologyIndian Institute of Technology RoorkeeRoorkeeIndia
  2. 2.Department of ChemistryIndian Institute of Technology RoorkeeRoorkeeIndia
  3. 3.Department of PharmacoinformaticsNIPERMohaliIndia
  4. 4.Department of Medicinal ChemistryNIPERMohaliIndia

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