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Asymmetrical mono-carbonyl ferrocenylidene curcumin and their dihydropyrazole derivatives: Which possesses the highest activity to protect DNA or scavenge radical?

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Abstract

A series of asymmetrical mono-carbonyl ferrocenylidene curcumin and their dihydropyrazole derivatives were synthesized. Their antioxidant abilities in protecting DNA against 2,2′-azobis(2-amidinopropane hydrochloride)-induced oxidation and scavenging 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS) radical were evaluated. In synthesis, the Michael addition reactions between phenylhydrazine and asymmetrical ferrocenylidene curcumin derivatives exhibit evident regioselectivity. The direction of addition depends on whether the benzene ring is substituted or not. The antioxidant abilities of compounds will increase when the ferrocenyl group is introduced. Moreover, such improvement derived from ferrocenyl group is also related to other substituent groups in molecule, not independent. Interestingly, p-dimethylamino group which is never considered as an active group, however, exhibits the best activity in protecting DNA and scavenging ABTS radical.

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References

  • Aeschbach R, Löliger J, Scott BC, Murcia A, Butler J, Halliwell B, Aruoma OI (1994) Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chem Toxicol 32:31–36

    Article  CAS  PubMed  Google Scholar 

  • Arts MJTJ, Haenen GRMN, Voss HP, Bast A (2004) Antioxidant capacity of reaction products limits the applicability of the Trolox Equivalent Antioxidant Capacity (TEAC) assay. Food Chem Toxicol 42:45–49

    Article  CAS  PubMed  Google Scholar 

  • Bowry VW, Stocker R (1993) Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc 115:6029–6044

    Article  CAS  Google Scholar 

  • Esparza-Ruiz A, Herrmann C, Chen J, Patrick BO, Polishchuk E, Orvig C (2012) Synthesis and in vitro anticancer activity of ferrocenyl–aminoquinoline–carboxamide conjugates. Inorg Chim Acta 393:276–283

    Article  CAS  Google Scholar 

  • Esrefoglu M (2012) Experimental and clinical evidence of antioxidant therapy in acute pancreatitis. World J Gastroenterol 18:5533–5541

    Article  PubMed Central  PubMed  Google Scholar 

  • Feng JY, Liu ZQ (2009) Phenolic and enolic hydroxyl groups in curcumin: which plays the major role in scavenging radicals? J Agric Food Chem 57:11041–11046

    Article  CAS  PubMed  Google Scholar 

  • Galli F, Battistoni A, Gambari R, Pompella A, Bragonzi A, Pilolli F, Iuliano L, Piroddi M, Dechecchi MC, Cabrini G (2012) Oxidative stress and antioxidant therapy in cystic fibrosis. Biochim Biophys Acta 1822:690–713

    Article  CAS  PubMed  Google Scholar 

  • Golikov AG, Kriven’ko AP, Bugaev AA, Fomina YA, Solodovnikov SF (2007) Molecular and crystal structures of 3-(4-bromphenyl)-7-furfurylidene-3,3a,4,5,6,7-hexahydro(2H)indazole. J Struct Chem 48:589–592

    Article  CAS  Google Scholar 

  • Gupta SC, Kismali G, Aggarwal BB (2012) Curcumin, a component of turmeric: from farm to pharmacy. BioFactors 39:2–13

    Article  Google Scholar 

  • Kelkel M, Jacob C, Dicato M, Diederich M (2010) Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules 15:7035–7074

    Article  CAS  PubMed  Google Scholar 

  • Labbozzetta M, Baruchellob R, Marchetti P, Guelic MC, Pomaa P, Notarbartoloa M, Simonib D, D’Alessandroa N (2009) Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin: implications for their antitumor and chemosensitizing activities. Chem Biol Interact 181:29–36

    Article  CAS  PubMed  Google Scholar 

  • Li PZ, Liu ZQ (2011) Ferrocenyl-substituted curcumin: can it influence antioxidant ability to protect DNA. Eur J Med Chem 46:1821–1826

    Article  CAS  PubMed  Google Scholar 

  • Li PZ, Liu ZQ (2013) Ferrocenyl-contained dendritic-like antioxidants with dihydropyrazole and pyrazole as the core: investigations into the role of ferrocenyl group and structure–activity relationship on scavenging radical and protecting DNA. Tetrahedron 69:9898–9905

    Article  CAS  Google Scholar 

  • Li XF, Jin C, He J, Zhou J, Wang HT, Dai B, Yan D, Wang JB, Zhao YL, Xiao XH (2012) Microcalorimetric investigation of the antibacterial activity of curcumin on Staphylococcus aureus coupled with multivariate analysis. J Therm Anal Calorim 109:395–402

    Article  CAS  Google Scholar 

  • Mahajan A, Kremer L, Louw S, Guéradel Y, Chibale K, Biot C (2011) Synthesis and in vitro antitubercular activity of ferrocene-based hydrazones. Bioorg Med Chem Lett 21:2866–2868

    Article  CAS  PubMed  Google Scholar 

  • Mahera P, Akaishi T, Schubert D, Abeb K (2010) A pyrazole derivative of curcumin enhances memory. Neurobiol Aging 31:706–709

    Article  Google Scholar 

  • Manohar S, Khan SI, Kandi SK, Raj K, Sun GJ, Yang XC, Calderon Molina AD, Ni NT, Wang BH, Rawat DS (2013) Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin. Bioorg Med Chem Lett 23:112–116

    Article  CAS  PubMed  Google Scholar 

  • Munoz-Munoz JL, Garcia-Molina F, Varon R, Tudela J, García-Cánovas F, Rodriguez-Lopez JN (2010) Quantification of the antioxidant capacity of different molecules and their kinetic antioxidant efficiencies. J Agric Food Chem 58:2062–2070

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Quirante J, Dubar F, González A, Lopez C, Cascante M, Cortés R, Forfar I, Pradines B, Biot C (2011) Ferrocene indole hybrids for cancer and malaria therapy. J Organomet Chem 696:1011–1017

    Article  CAS  Google Scholar 

  • Rahman I, MacNee W (2012) Antioxidant pharmacological therapies for COPD. Curr Opin Pharmacol 12:256–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237

    Article  CAS  PubMed  Google Scholar 

  • Sahu PK, Sahu PK, Gupta SK, Thavaselvamd D, Agarwal DD (2012) Synthesis and evaluation of antimicrobial activity of 4H-pyrimido[2,1-b] benzothiazole, pyrazole and benzylidene derivatives of curcumin. Eur J Med Chem 54:366–378

    Article  CAS  PubMed  Google Scholar 

  • Sardjiman SS, Reksohadiprodjo MS, Hakim L, van der Goot H, Timmerman H (1997) 1,5-Diphenyl-1,4-pentadiene-3-ones and cyclic analogues as antioxidative agents. Synthesis and structure–activity relationship. Eur J Med Chem 32:625–630

    Article  CAS  Google Scholar 

  • Shao J, Geacintov NE, Shafirovich V (2010) Oxidative modification of guanine bases initiated by oxyl radicals derived from photolysis of azo compounds. J Phys Chem B 114:6685–6692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shehzad A, Rehman G, Lee YS (2013) Curcumin in inflammatory diseases. BioFactors 39:69–77

    Article  CAS  PubMed  Google Scholar 

  • Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64:353–356

    Article  CAS  PubMed  Google Scholar 

  • Xiao C, Luo XY, Li DJ, Lu H, Liu ZQ, Song ZG, Jin YH (2012) Synthesis of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety to scavenge radicals and to protect DNA. Eur J Med Chem 53:159–167

    Article  CAS  PubMed  Google Scholar 

  • Zennaro L, Rossetto M, Vanzani P, Marco VD, Scarpa M, Battistin L, Rigo A (2007) A method to evaluate capacity and efficiency of water soluble antioxidants as peroxyl radical scavengers. Arch Biochem Biophys 462:38–46

    Article  CAS  PubMed  Google Scholar 

  • Zhao F, Liu ZQ (2009) The protective effect of hydroxyl-substituted Schiff bases on the radical-induced oxidation of DNA. J Phys Org Chem 22:791–798

    Article  CAS  Google Scholar 

  • Zsoldos-Mády V, Ozohanics O, Csámpai A, Kudar V, Frigyes D, Sohár P (2009) Ferrocenyl pyrazolines: preparation, structure, redox properties and DFT study on regioselective ring-closure. J Organomet Chem 694:4185–4195

    Article  Google Scholar 

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Acknowledgments

Financial support from Jilin Provincial Science and Technology Department, China, is acknowledged gratefully (20130206075GX).

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Authors and Affiliations

  1. Department of Organic Chemistry, College of Chemistry, Jilin University, No. 2519 Jiefang Road, Changchun, 130021, China

    Pei-Ze Li & Zai-Qun Liu

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  1. Pei-Ze Li
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  2. Zai-Qun Liu
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Correspondence to Zai-Qun Liu.

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Li, PZ., Liu, ZQ. Asymmetrical mono-carbonyl ferrocenylidene curcumin and their dihydropyrazole derivatives: Which possesses the highest activity to protect DNA or scavenge radical?. Med Chem Res 23, 3478–3490 (2014). https://doi.org/10.1007/s00044-014-0924-1

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  • DOI: https://doi.org/10.1007/s00044-014-0924-1

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