Evaluation of Antinociceptive and Anti-Inflammatory Effects of Synthetic O-Prenylated Phenolic Derivatives

Niraldo Paulino, Amarilis Scremin Paulino, Priscila Vaultier, Laura Pisco, Carolina Passarelli, José Matheus de Freitas Costa, Dirk Michalik, Paulo Celso Pardi, José Agustín Quincoces Suárez

Grupo de Pesquisa e Desenvolvimento de Biomedicamentos (BIOMED), Programa de Mestrado Profissional em Farmácia, Universidade Bandeirante de S?o Paulo, Rua Maria Candida 1813, S?o Paulo/SP – Brasil;.
Laboratório de Controle de Qualidade, Universidade Federal de Santa Catarina, Florianópolis, SC – Brasil;.
Laboratório de Síntese Organica, Universidade Bandeirante de S?o Paulo, Rua Maria Candida 1813, S?o Paulo/SP – Brasil;.
Leibniz-Institut für Katalyse an der Universit?t Rostock, Rostock, Germany..

DOI: 10.4236/pp.2012.33047                

Abstract

This work describes the synthesis, antinociceptive and anti-inflammatory effect of O-prenyl derivatives: O-prenyl derivatives 2-(3-methylbut-2-enyloxy)acetophenone (L1) and 3-methoxy-4-(3-methylbut-2-enyloxy)benzaldehyde (V1). Treatment with L1- or V1-produced antinociceptive effect on classical pain models: acetic acid abdominal contortions and formalin test (first and second phases), and in hot plate or tale flick models in mice without changing the locomotors performance, and anti-oedematogenic or anti-inflammatory effect in vivo: carrageenan-induced paw oedema and peritonitis in mice. In addition, L1 and V1 derivatives reduced nitric oxide production on RAW 264.7 cells stimulated with lipopolysaccharide without changing the cell viability. Taken together, our results show for the first time that L1 and V1 can produce antinociception and modulate inflammatory response when administered in mice.

Keywords

Anti-Inflammatory; Antinociception; Synthesis; O-Prenyl Compounds

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	H. Süleyman, B. Demircan and Y. Karag?z, “Anti-Inflammatory and Side Effects of Cyclooxygenase Inhibitors,” Pharmacological Reports, Vol. 59, No. 3, 2007, pp. 247-258.
[2]	J. R. Vane and R. M. Botting, “Anti-Inflammatory Drugs and Their Mechanism of Action,” Inflammation Research, Vol. 47, Suppl. 2, 1998, pp. S78-S87. doi:10.1007/s000110050284
[3]	K. D. Rainsford, “Anti-Inflammatory Drugs in the 21st Century,” Subcell Biochemistry, Vol. 42, 2007, pp. 3-27. doi:10.1007/1-4020-5688-5_1
[4]	G. Appendino, S. Tagliapietra, G. Cravotto and M. Gian, “Structure and Synthesis of a Prenylated Acetophenone from Ferula communis L.,” Gazzeta Chimica Italiana, Vol. 119, 1998, pp. 385-388.
[5]	L. Pisco, M. Kordian, K. Peseke, H. Feist, D. Michalik, E. Estrada, J. Carvalho, G. Hamilton, D. Rando and J. Quincoces, “Synthesis of Compounds with Antiproliferative Activity as Analogues of Prenylated Natural Products Existing in Brazilian Propolis,” European Journal of Medicinal Chemistry, Vol. 41, No. 3, 2006, pp. 401-407. doi:10.1016/j.ejmech.2005.10.020
[6]	J. Quincoces Suárez, M. G. Jasiulionis, R. P. Santos, P. C. Pardi, D. G. Rando, M. R. Machado, C. Valduga and D. A. Maria, “Compostos Derivados de 4-Hidroxi-3- metoxi-benzaldeído, Processo de Obten??o, Composi??o Farmacêutica, uso de um ou Mais Compostos,” Brazilian Patent PI 0803375-7, 2008.
[7]	M. C. Marcucci, F. Ferreres, C. García-Viguera, V. S. Bankova, S. L. De Castro, A. P. Dantas, P. H. Valente and N. Paulino, “Phenolic Compounds from Brazilian Propolis with Pharmacological Activities,” Journal of Ethnopharmacology, Vol. 74, No. 2, 2001, pp. 105-112. doi:10.1016/S0378-8741(00)00326-3
[8]	G. Appendino, E. Mercalli, N. Fuzzati, L. Arnoldi, M. Stavri, S. Gibbons, M. Ballero and A. Maxia, “Antimycobacterial Coumarins from the Sardinian Giant Fennel (Ferula communis),” Journal of Natural Products, Vol. 67, No. 12, 2004, pp. 2108-2110. doi:10.1021/np049706n
[9]	E. Cunha, “Isolation of 3-[4-(3-Methyl-but-2-enyloxy)- phenyl]-acrylic Acid Methyl Ester from Aerial Parts of Eriostemon auslalasius Pers. Subsp. Banksii,” Australian Journal of Chemistry, Vol. 46, No. 10, 1993, pp. 1507- 1514.
[10]	N. Paulino, S. R. Abreu, Y. Uto, D. Koyama, H. Nagasawa, H. Hori, V. M. Dirsch, A. M. Vollmar, A. Scremin and W. Bretz, “Anti-Inflammatory Effects of a Bioavailable Compound, Artepillin C, in Brazilian Propolis,” European Journal of Pharmacology, Vol. 587, No. 1-3, 2008, pp. 296-301. doi:10.1016/j.ejphar.2008.02.067
[11]	M. Zimmermann, “Ethical Guidelines for Investigations of Experimental Pain in Conscious Animals,” Pain, Vol. 16, 1983, pp. 109-110. doi:10.1016/0304-3959(83)90201-4
[12]	R. O. de Cam-pos, N. Paulino, C. H. da Silva, A. Scremin and J. B. Ca-lixto, “Anti-Hyperalgesic Effect of an Ethanolic Extract of Propolis in Mice and Rats,” Journal of Pharmacy and Pharmacology, Vol. 50, No. 10, 1998, pp. 1187-1193. doi:10.1111/j.2042-7158.1998.tb03333.x
[13]	C. R. Corrêa and J. B. Calixto, “Evidence for Participation of B1 and B2 Kinin Receptors in formalin-Induced Nociceptive Response in the Mouse,” British Journal of Pharmacology, Vol. 110, No. 1, 1993, pp. 193-198.
[14]	N. B. Eddy and D. Leimbach, “Synthetic Analgesics. II. Dithienylbutenyl- and Dithienylbutylamines,” The Journal of Pharmacology and Experimental Therapeutics, Vol. 107, No. 3, 1953, pp. 385-393.
[15]	E. Wei, “Morphine Analgesia, Tolerance and Physical Dependence in the Adrenalectomized Rat,” British Journal of Pharmacology, Vol. 47, No. 4, 1973, pp. 693-699.
[16]	K. S. Tratsk, M. M. Campos, Z. R. Vaz, V. C. Filho, V. Schlemper, R. A. Yunes and J. B. Calixto, “Anti-Allergic Effects and Oedema Inhibition Caused by the Extract of Drymis winteri,” Inflammation Research, Vol. 46, No. 12, 1997, pp. 509-514. doi:10.1007/s000110050234
[17]	J. C. T. Carvalho, L. S. Santos, E. P. Viana, S. S. M. S. De Almeide, E. Marconato, M. Rodrigues, L. R. Ferreira and A. Van De Kamp, “Anti-Inflammatory and Analgesic Activities of the Crude Extracts from Stem Bark on Bauhinia guianensis,” Pharmaceutical Biology, Vol. 37, 1999, pp. 281-284. doi:10.1076/phbi.37.4.281.5803
[18]	V. N. Sumantran, “Cellular Chemosensitivity Assays: An Overview,” Methods in Molecular Biology, Vol. 731, 2011, pp. 219-236. doi:10.1007/978-1-61779-080-5_19
[19]	D. Sachs, F. Q. Cunha, S. Poole and S. H. Ferreira, “Tumour Necrosis Factor-Alpha, Interleukin-1beta and Interleukin-8 Induce Persistent Mechanical Nociceptor Hy-persensitivity,” Pain, Vol. 96, No. 1-2, 2002, pp. 89-97. doi:10.1016/S0304-3959(01)00433-X
[20]	R. A. Ribeiro, M. L. Vale, S. M. Thomazzi, A. B. Paschoalato, S. Poole, S. H. Ferreira and F. Q. Cunha, “Involvement of Resident Macrophages and Mast Cells in the Writhing Nociceptive Response Induced by Zymosan and Acetic Acid in Mice,” European Journal of Pharmacology, Vol. 387, No. 1, 2000, pp. 111-118. doi:10.1016/S0014-2999(99)00790-6
[21]	C. J. Morris, “Carrageenan-Induced Paw Edema in the Rat and Mouse,” Methods in Molecular Biology, Vol. 225, 2003, pp. 115-121.
[22]	P. Crunkhorn and S. C. Meacock, “Mediators of the Inflammation Induced in the Rat Paw by Carrageenin,” British Journal of Pharmacolology, Vol. 42, No. 3, 1971, pp. 392-402.
[23]	C. Cayla, D. Labuz, H. Machelska, M. Bader, M. Sch?fer and C. Stein, “Impaired Nociception and Peripheral Opioid Antinociception in Mice Lacking Both kinin B1 and B2 Receptors,” Anes-thesiology, Vol. 116, No. 2, 2012, pp. 448-457. doi:10.1097/ALN.0b013e318242b2ea
[24]	M. Barth, M. Bondoux, J. M. Luccarini, V. Peyrou, P. Dodey, D. Pruneau, C. Massardier and J. L. Paquet, “From Bra-dykinin b2 Receptor Antagonists to Orally Active and Selective Bradykinin b1 Receptor Antagonists,” Journal of Medicinal Chemistry, Vol. 55, No. 6, 2012, pp. 2574-2584. doi:10.1021/jm2016057
[25]	S. P. Sardi, V. Rey-Ares, V. A. Pujol-Lereis, S. A. Serrano and R. P. Rothlin, “Further Pharmacological Evidence of Nuclear Factor-Kappa B Pathway Involvement in Bradykinin B1 Receptor-Sensitized Responses in Human Umbilical Vein,” The Journal of Pharmacology and Experimental Therapeutics, Vol. 301, No. 3, 2002, pp. 975-980. doi:10.1124/jpet.301.3.975