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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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
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
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
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
Esrefoglu M (2012) Experimental and clinical evidence of antioxidant therapy in acute pancreatitis. World J Gastroenterol 18:5533–5541
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
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
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
Gupta SC, Kismali G, Aggarwal BB (2012) Curcumin, a component of turmeric: from farm to pharmacy. BioFactors 39:2–13
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
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
Li PZ, Liu ZQ (2011) Ferrocenyl-substituted curcumin: can it influence antioxidant ability to protect DNA. Eur J Med Chem 46:1821–1826
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
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
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
Mahera P, Akaishi T, Schubert D, Abeb K (2010) A pyrazole derivative of curcumin enhances memory. Neurobiol Aging 31:706–709
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
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
Pan MH, Huang TM, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27:486–494
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
Rahman I, MacNee W (2012) Antioxidant pharmacological therapies for COPD. Curr Opin Pharmacol 12:256–265
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
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
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
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
Shehzad A, Rehman G, Lee YS (2013) Curcumin in inflammatory diseases. BioFactors 39:69–77
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
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
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
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
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
Financial support from Jilin Provincial Science and Technology Department, China, is acknowledged gratefully (20130206075GX).
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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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