Evaluation and Theoretical Study on the Anti-inflammatory Mechanism of 1-Nitro-2-phenylethane

Abstract

In this study, 1-nitro-2-phenylethane was evaluated with respect to its effects in edema models of acute inflammation induced with carrageenan, dextran, and croton oil. 1-Nitro-2-phenylethane produced inhibition of rat paw edema induced by carrageenan and dextran at the doses of 25 and 50 mg/kg. The same doses caused an inhibition of croton oil-induced ear edema in mice. Our results suggest that 1-nitro-2-phenylethane has anti-inflammatory activity, probably of peripheral origin, acting in the synthesis and/or release of inflammatory mediators. A conformational study of 1-nitro-2-phenylethane was carried out using density functional theory calculations, showing three different groups of conformers corresponding to energy minimum geometries. The stereoelectronic repulsions are responsible for conformational preferences and the one most stable conformer. The prostaglandin endoperoxide synthase mechanism is related more to electrophilic than nucleophilic properties.

Key words

anti-inflammatory - Lauraceae - Aniba canelilla - DFT - 1-nitro-2-phenylethane - SAR

• References

• 1 Maia JGS, Zoghbi MGB, Andrade EHA. Plantas aromáticas na Amazônia e seus óleos essenciais. 1st. edition, Volume 1. Belém: Museu Paraense Emílio Goeldi; 2001
• 2 Naranjo P, Kijjoa A, Giesbrecht A, Gottlieb OR. Ocotea quixos, American cinnamon. J Ethnopharmacol 1981; 4: 233-236
• 3 Taveira FSN, De Lima WN, Andrade EHA, Maia JGS. Seasonal essential oil variation of Aniba canelilla . Biochem Syst Ecol 2003; 31: 69-75
• 4 Lima AB, Santana MB, Cardoso AS, Silva JKR, Maia JGS, Carvalho JCT, Sousa PJC. Antinociceptive activity of 1-nitro-2-phenylethane, the main component of Aniba canelilla essential oil. Phytomedicine 2009; 16: 555-559
• 5 Interaminense LFL, Siqueira RJB, Xavier FE, Duarte GP, Magalhães PJC, Silva JK, Maia JGS, Sousa PJC, Leal-Cardoso JH, Lahlou S. Cardiovascular effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in spontaneously hypertensive rats. Fund Clin Pharmacol 2011; 25: 661-669
• 6 Siqueira RJB, Macedo FIB, Interaminense LFL, Duarte GP, Magalhães PJC, Brito TS, Silva JKR, Maia JGS, Sousa PJC, Leal-Cardoso JH, Lahlou S. 1-Nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, elicits a vago-vagal bradycardiac and depressor reflex in normotensive rats. Eur J Pharmacol 2010; 638: 90-98
• 7 Tubaro A, Dri P, DelBello G, Zilli C, Della Loggia R. The croton oil ear test revisited. Agents Actions 1985; 17: 347-349
• 8 Carvalho JCT, Teixeira JRM, Souza PJC, Bastos JK, Filho DDS, Sarti SJ. Preliminary studies of analgesic and anti-inflammatory properties of Caesalpinia ferrea crude extract. J Ethnopharmacol 1996; 53: 175-178
• 9 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr. JA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA. Gaussian 03, Revision C.02. Wallingford: Gaussian, Inc.; 2004
• 10 Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 1988; 37: 785-789
• 11 Miehlich B, Savin A, Stoll H, Preuss H. Results obtained with the correlation energy density functionals of Becke and Lee, Yang and Par. Chem Phys Lett 1989; 157: 200-206
• 12 Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 1993; 98: 5648-5652
• 13 Becke AD. A new mixing of Hartree–Fock and local density-functional theories. J Chem Phys 1993; 98: 1372-1377
• 14 Hariharan PC, Pople JA. Influence of polarization functions on MO hydrogenation energies. Theor Chim Acta 1973; 28: 213-222
• 15 Boys SF, Bernardi F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 1970; 19: 553-566
• 16 Kohn W, Becke AD, Parr RG. Density functional theory of electronic structure. J Phys Chem 1996; 100: 12974-12980
• 17 Parr RG, Pearson RG. Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc 1983; 105: 7512-7516
• 18 Parr RG, Szentpaly LV, Liu S. Electrophilicity Index. J Am Chem Soc 1999; 121: 1922-1924
• 19 Chattaraj PK, Lee H, Parr RG. HSAB principle. J Am Chem Soc 1991; 113: 1855-1856
• 20 Silva JKR, Sousa PJC, Andrade EHA, Maia JGS. Antioxidant capacity and cytotoxicity of essential oil and methanol extract of Aniba canelilla (H.B.K.) Mez. J Agric Food Chem 2007; 55: 9422-9426
• 21 Lahlou S, Magalhães PJ, de Siqueira RJ, Figueiredo AF, Interaminense LFL, Maia JGS, Sousa PJC. Cardiovascular effects of the essential oil of Aniba canelilla bark in normotensive rats. J Cardiovasc Pharmacol 2005; 46: 412-421
• 22 Oger JM, Richomme P, Guinaudeau H, Bouchara JP, Fournet A. Aniba canelilla (H.B.K.) Mez essential oil: analysis of chemical constituents, fungistatic properties. J Essent Oil Res 1994; 6: 493-497
• 23 Bin Z, Jian-Bei L, Dong-Ming Z, Ding Y, Guan-Hua D. Analgesic and anti-inflammatory activities of a fraction rich in gaultherin isolated from Gaultheria yunnanensis (Franch.) Rehder. Biol Pharm Bull 2007; 30: 465-469
• 24 Singh S, Khajuria A, Taneja SC, Johri RK, Singh J, Qazi GN. Boswellic acids: A leukotriene inhibitor also effective through topical application in inflammatory disorders. Phytomedicine 2008; 15: 400-407
• 25 Inoue H, Mori T, Shibata Y. Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear edema. Br J Pharmacol 1989; 96: 204-210
• 26 Young JM, De Young LM. Cutaneous models of inflammation for the evaluation of topical and systemic pharmacological agents. In: Chang JY, Lewis AJ, editors Pharmacological methods in the control of inflammation. New York: Alan R. Liss; 1989: 215-231
• 27 Mbiantcha M, Kamanyi A, Teponno RB, Tapondjou AL, Watcho P, Nguelefack TB. Analgesic and anti-inflammatory properties of extracts from the bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in mice and rats. Evid Based Complement Alternat Med 2011; 912935: 1-9
• 28 Haarmann A, Deiß A, Prochaska J, Foerch C, Weksler B, Romero I, Couraud PO, Stoll G, Rieckmann P, Buttmann M. Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown. PLoS One 2010; 5: 1-10
• 29 Hehre WJ, Radom L, Schleyer PVR, Pople JA. AB INITIO molecular orbital theory. New York: Wiley; 1986
• 30 Wilson KJ, Derreumaux P, Vergoten G, Peticolas WL. Conformational studies of neuroactive ligands. 2. Solution-state conformations of acetylcholine. J Phys Chem 1989; 93: 1351-1357
• 31 Cushley RJ, Mautner HG. NMR studies on the conformation of acetylcholine isologues. Tetrahedron 1970; 26: 2151-2159
• 32 Chothia C, Pauling P. Conformations of acetylcholine. Nature 1968; 219: 1156-1157
• 33 Kulmacz RJ, Palmer G, Tsai AL. Prostaglandin H synthase: perturbation of the tyrosyl radical as a probe of anticyclooxygenase agents. Mol Pharmacol 1991; 40: 833-837
• 34 Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. 1. Acetylation of a particulate fraction protein. J Clin Invest 1975; 56: 624-632
• 35 Diniz JEM, Borges RS, Alves CN. A DFT study for paracetamol and 3,5-disubstituted analogues. J Mol Struct 2004; 673: 93-97
• 36 Silva JR, Queiroz LMD, Queiroz AN, Souza PJC, Borges RS. A theoretical study of paracetamol acyl-ether derivatives. J Comp Theor Nanosci 2011; 8: 670-675
• 37 Freire ADT, Landivar LMC, Queiroz AN, Borges RS. A Theoretical Study for Oxidative Metabolism of Salicylates. J Comp Theor Nanosci 2009; 6: 1140-1142
• 38 Borges RS, Mendes APS, Silva BHS, Alves CN, Nascimento JLM. A theoretical study of salicylate oxidation for ADME prediction. Med Chem Res 2011; 20: 269-273
• 39 Kankaanranta H, Ilmarinen P, Zhang X, Nissinenand E, Moilanen E. Antieosinophilic activity of orazipone. Mol Pharmacol 2006; 69: 1861-1870