Synthesis and anti-ulcer activity of new derivatives of glycyrrhetic, oleanolic and ursolic acids

Farmaco

Volumn 53, Issue 1, 1999, Pages 22-32

  Farina, Carlo ^a   Pinza, Mario ^b   Pifferi, Giorgio ^c  

^a SmithKline Beecham SpA   (Italy)

^b Università Politecnica delle Marche ACRAF Gruppo Angelini   (Italy)

^c Istituto di Chimica Farmaceutica e Tossicologica   (Italy)

Author keywords

Amyrin; Anti ulcer; Cytoprotection; Glycyrrhetic acid; Mineralocorticoid; Oleanolic acid; Pentacyclic triterpenes; Ursolic acid

Indexed keywords

ALCOHOL; ALDOSTERONE; ALPHA AMYRIN; ANTIULCER AGENT; BETA AMYRIN; CARBENOXOLONE; GLYCYRRHETINIC ACID DERIVATIVE; KETONE; MINERALOCORTICOID; OLEANOLIC ACID DERIVATIVE; PROSTAGLANDIN E2; URSOLIC ACID DERIVATIVE;

DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; LIVER TOXICITY; MONKEY; NEPHROTOXICITY; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; ULCER;

ANIMALS; ANTI-ULCER AGENTS; GLYCYRRHETINIC ACID; MICE; OLEANOLIC ACID; RATS; TRITERPENES;

EID: 0344938259     PISSN: 0014827X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0014-827X(97)00013-X     Document Type: Review

References (55)

1. [1] Herba Regolitia, in: Erbario Redi, XV Century, p. 165.
2. [2] K.R. Kirtikar, B.D. Basu, in Indian Medicinal Plants, vol. I, Leader Road, Allahabad, 1944, p. 727.
3. [3] P. Karrer, W. Karrer, J.C. Chao, Glukoside. VIII. Beitrag zur kenntnis des glycyrrhizins, Helv. Chim. Acta 4 (1921) 100.
4. [4] R.S.H. Finney, A.L. Tarknoy, The pharmacological properties of glycyrrhetinic acid hydrogen succinate, J. Pharm. Pharmacol. 12 (1960) 49-58.
5. [5] S. Tanaka, C. Uno, M. Akimoto, M. Tabata, C. Honda, W. Kamisako, Anti-allergic effect of bryonolic acid from Luffa cylindrica cell suspension culture, Planta Med. 57 (1991) 527-530.
6. [6] M.H. Khan, F.M. Sullivan, in: J. Robson, F. Sullivan (Eds.), Symposium on Carbenoxolone, Butterworths, London, 1968, p. 5.
7. [7] E.Z. Dajani, R.G. Bianchi, J.J. Casler, J.F. Weet, Gastric antiulcer and antisecretory effects of carbenoxolone, aldosterone and desoxycorticosterone in rats, Arch. Int. Pharmacodyn. 242 (1979) 128-138.
8. [8] H. Inoue, S. Kurosu, T. Takeuchi, T. Mori, S. Shibata, Glycyrrhetinic acid derivatives: anti-nociceptive activity of deoxoglycyrrhetol dihemiphthalate and the related compounds, J. Pharm. Pharmacol. 42 (1990) 199-200.
9. [9] H. Nishino, A. Nishino, J. Takayasu, T. Hasegawa, A. Iwashima, K. Hirabayashi, S. Iwata, S. Shibata, Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds, Cancer Res. 48 (1988) 5210-5215.
10. [10] D.H. Miles, U. Kokpol, L.H. Zalkow, S.J. Steindel, J.B. Nabors, Tumor inhibitors. I. Preliminary investigation of antitumor activity of Sarracenia flava, J. Pharmacol. Sci. 63 (1974) 613-615.
11. [11] C. Serra, G. Lampis, R. Pompei, M. Pinza, Antiviral activity of new triterpenic derivatives, Pharmacol. Res. 29 (1994) 359-366.
12. [12] D.J. Dargan, J.H. Subak-Sharpe, The effect of triterpenoid compounds on uninfected and Herpes Simplex Virus-infected cells in culture. I. Effect an cell growth, virus particles and virus replication, J. Gen. Virol. 66 (1985) 1771-1784.
13. [13] G. Pinducciu, C. Serra, M.G. Cagetti, M. Cotti, D. Deidda, M. Pinza, R. Pompei, Selective antimicrobial activity of triterpene derivatives on oral bacteria, Med. Microbiol. Lett. 4 (1995) 83-90.
14. [14] G. Subba Rao, J.E. Sinsheimer, K.W. Cochran, Antiviral activity of triterpenoid saponins containing acylated β-amyrin aglycones, J. Pharmacol. Sci. 63 (1974) 471-473.
15. [15] A.R. Helbing, I.G. Berntsen, On the action mechanism of glycyrrhetic acid, Pharm. Weekblad 100 (1965) 1438-1441.
16. [16] S. Gottfried, L. Baxendale, Glycyrrhetinic acid derivatives, Br. Patent No. 843 133 (1960); Chem. Abstr. 55 (1960) 2027i.
17. [16] S. Gottfried, L. Baxendale, Glycyrrhetinic acid derivatives, Br. Patent No. 843 133 (1960); Chem. Abstr. 55 (1960) 2027i.
18. [17] J.H. Baron, F.M. Sullivan (Eds.), Carbenoxolone Sodium, Butterworths, London, 1970.
19. [18] R. Doll, M.J.S. Langman, H.H. Shawdon, Treatment of gastric ulcer with carbenoxolone: antagonistic effect of spironolactone, Gut 9 (1968) 42-45.
20. 4-5α-and 5β-reductase in rat liver, Arzneim, Forsch. 29 (1979) 647-649.
21. [20] L.M. Atherden, Studies with glycyrrhetic acid: inhibition of metabolism of steroids in vitro, Biochem. J. 69 (1958) 75-78.
22. [21] J.S. Baran, D.D. Langford, Chi-Dean Liang, B.S. Pitzele, Synthesis and biological activities of substituted glycyrrhetic acids, J. Med. Chem. 17 (1974) 184-191, and Refs. therein.
23. [22] W. Logemann, F. Lauria, G. Tosolini, Über ketole der 18α-und 18β-glycyrrhetinsäure, Chem. Ber. 90 (1957) 601-604.
24. [23] H. Shay, S.A. Komarov, M. Siplet, S.S. Fels, D. Meranze, H. Gruenstein, A simple method for the uniform production of gastric ulceration in the rat, Gastroenterology 5 (1945) 43.
25. [24] C.M. Kagawa, Blocking the renal electrolyte effects of mineralocorticoids with an orally active steroidal spirolactone, Endocrinology 67 (1960) 125-132.
26. [25] L. Canonica, B. Danieli, P. Manitto, G. Russo, E. Bombardelli, Triterpeni della glycyrrhiza glabra - Nota V. Glicirretolo e 21α-idrossiisoglabrolide, Gazz. Chim. Ital. 97 (1967) 1347-1358.
27. [26] A.A. Ryabinin, N.E. Konovalova, Syntheses based on glycyrrhetic acid, Zh. Obshch. Klin. 32 (1962) 644-646.
28. [27] K. Takahashi, S, Shibata, S. Yano, M. Harada, H. Saito, Y. Tamura, A. Kumagai, Chemical modification of glycyrrhetinic acid in relation to the biological activities, Chem. Pharm. Bull. 28 (1980) 3449-3452.
29. [28] D. Braga, M. Contento, G. Pifferi, A, Umani Ronchi, New derivatives of glycyrrhetic acid, 2nd Eur. Symp. Organic Chemistry, Stresa, Italy, 1-5 June 1981, Abstr. 58C.
30. [29] G. Pifferi, A. Umani Ronchi, C. Farina, A. Gamba, 3β-Hydroxy-18β-olean-9-en-30-oic acids, US Patent No. 4 173 648 (1979); Chem. Abstr. 90 (1979) 23334j.
31. [29] G. Pifferi, A. Umani Ronchi, C. Farina, A. Gamba, 3β-Hydroxy-18β-olean-9-en-30-oic acids, US Patent No. 4 173 648 (1979); Chem. Abstr. 90 (1979) 23334j.
32. [30] R. Pellegata, Reduction of the enone syslem of glycyrrhetic acid, manuscript in preparation.
33. [31] R. Pellegata, M. Pinza, G. Pifferi, G. Clavenna, Synthesis and pharmacological activity of a new unsaturated analogue of carbenoxolone, North. Am. Med. Chem. Symp., Toronto, Canada, 20-24 June 1982, Abstr. P.85.
34. [32] C. Farina, M. Pinza, A. Umani Ronchi, G. Pifferi, Derivati sintetici della β-amirina ad attività biologica, II Congr. Naz. Sostanze Organiche Naturali nell'Industria Chimica, Pisa, Italy, 23-26 May 1983, Abstr. P.29.
35. [33] S. Irwin, Comprehensive observational assessment: 1a. A systematic, quantitative procedure for assessing the behavioural and physiologic state of the mouse, Psycopharmacologia (Berl.) 13 (1968) 222-257.
36. [34] M. Pinza, G. Pifferi, R. Pellegata, G. Clavenna, Synthesis, antiulcer and mineralocorticoid activity of a new unsaturated analogue of carbenoxolone, North Am. Med. Chem. Symp., Toronto, Canada, 20-24 June 1982, Abstr. P.86.
37. [35] G. Clavenna, R. Musci, S. Oneta, L. Dorigotti, Antiulcer and mineralocorticoid activities of ISF 2715: a new carbenoxolone analogue, Abstr., 7th Congr. Digestive Endoscopy, Stockholm, Sweden, 14-19 June 1982.
38. [36] G. Clavenna, R. Musci, L. Dorigotti, Antiulcer and mineralocorticoid activities of carbenoxolone and desoxycorticosterone in rats. J. Pharm. Pharmacol. 34 (1982) 517-519.
39. [37] G.P. Velo, P. Minuz, A. Riela, G. Brocco, M. Degan, L. Franco, G. Cavallini, Gastric and systemic effect of carbenoxolone and its derivative ISF 2715 in humans, Adv. Prostaglandin, Thromboxane and Leukotriene Res. 17 (1987) 361-365.
40. [38] U. Wrzeciono, I. Malecki, J. Budzianowski, H. Kierylowjcks, L. Zaprutko, E. Beimcik, H. Kostepska, Nitrogenous triterpene derivatives. Part 10: Hemisuccinates of some derivatives of oleanolic acid and their antiulcer effects, Pharmazie 40 (1985) 542-544.
41. [39] S. Shibata, K. Takahashi, S. Yano, M, Harada, H. Saito, Y. Tamura, A. Kumagai, K. Hirabayashi, M. Yamamoto, N. Nagata, Chemical modifications of glycyrrhettnic acid in relation to biological activities, Chem. Pharm. Bull. 35 (1987) 1910-1918.
42. [40] S. Yano, M. Harada, K. Watanabe, K. Nakamaru, Y. Hatekeyama, S. Shibata, K. Takahashi. T. Mori, K. Hirabayashi, M. Takeda, N. Nagata, Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models, Chem. Pharm. Bull. 37 (1989) 2500-2504.
43. [41] Y. Hatakeyama, S. Yano, K. Watanabe, Successive measurements of gastric mucus secretion using rat in situ stomach preparation: evaluation of antiulcerous activity of drugs, Jpn. J. Pharmacol. 46 (1988) 292P, Abstr. P453.
44. [42] O. Jeger, R. Borth, L. Ruzicka, Oxydation von acetyl-ursolsäure mit wasserstoff peroxid, Helv. Chim. Acta 29 (1946) 1999-2006.
45. [43] C. Farina, personal communication.
46. [44] W. Manson, F.S. Sring, Triterpene resinols and related acids. Part XXIII. (a) The decarboxylation of acetylketoursolic acid. (b) The oxidation of methyl acetylursolate with hydrogen peroxide. J. Chem. Soc. (1951) 3332-3336.
47. [45] T. Mezzetti, G. Orzalesi, V. Bellavita, Chemistry of ursolic acid. Planta Med. 20 (1971) 244-252.
48. [46] G. Clavenna, C. Farina, M. Pinza, G, Pifferi, Pharmaceutically active ursolic acid derivatives, US Patent No. 4 530 934 (1985); Chem. Abstr. 101 (1985) 23779d.
49. [46] G. Clavenna, C. Farina, M. Pinza, G, Pifferi, Pharmaceutically active ursolic acid derivatives, US Patent No. 4 530 934 (1985); Chem. Abstr. 101 (1985) 23779d.
50. [47] R. Nizzola, S. Malandrino, G. Pifferi, Ursane derivatives, their preparation, and pharmaceutical formulation thereof as antiulcer agents, Eur. Patent Applic. No. 515 159 (1992); Chem. Abstr. 118 (1992) 102280p.
51. [47] R. Nizzola, S. Malandrino, G. Pifferi, Ursane derivatives, their preparation, and pharmaceutical formulation thereof as antiulcer agents, Eur. Patent Applic. No. 515 159 (1992); Chem. Abstr. 118 (1992) 102280p.
52. [48] A. Cristoni, R. Nizzola, S. Malandrino, G. Pifferi, Synthesis and antiulcer activity of uvaol hemiphthalate derivatives, Il Farmaco 49 (1994) 281-284.
53. [49] S. Malandrino, personal communication.
54. [50] G. Pifferi, R. Vitali, Medicines from plants, La Chimica e L'Industria 75 (1993) 380-384.
55. [51] G. Pifferi, Derivati della β-amirina ad attività antiulcera, Abstr., VII Conv. Naz. Soc. It. Farmacognosia, Bologna, Italy, 30 June-2 July 1994, p. 42.