Wybrane bioaktywne pochodne adamantanu

• Autorzy: Orzeszko A.

Warianty tytułu

EN

The choisen bioactive adamantane derivatives

• Języki publikacji: PL

Abstrakty

EN

In 1933 adamantane was isolated from petroleum of Czechoslovakia by Landa [2]. Its unique structure is reflected in highly unusual physical and chemical properties. For example this hydrocarbon has extraordinary high melting point 269oC. It was also shown that the bromination is an ionic process; it is catalyzed by Lewis acids and not by peroxides or light. Adamantane possesses a unique rigid, but strain-free ring system, composed of three fused chair cyclohexane rings. The other source of adamantane derivatives are organic syntheses including cyclization and rearrangement of hydrocarbons. Also, it was found that 1-adamantanol refluxed with trifluoroacetic acid and respective heterocycles yielded N-adamantylated compounds [6]. Particularly the biological properties of adamantane derivatives are very interesting. The most known of clinical use is the antiviral drug 1-amnoadamantane (amantadine) [7-11]. In the presented paper only antimicrobial, antiviral as well as anticancer agents are described. Novel ester imides synthesised from trimellitic acid chloride and 1-adamantanol, 2-adamantanol, 1-adamantanemethanol or 1-adamantaneethanol, were tested as antimicrobial compounds [16-18]. Some of these derivatives showed significant activity. The incorporation of L-alanine and L-phenylalanine aw well as ?-amino acids into the phthalimide moiety as N-substituents, leads to strong antimicrobial activity against Staphylococcus aureus strains. A variety of 5'-N-phtaloyl-3'-azido-2',3'-dideoxythymidine derivatives has been synthesised and evaluated for their activity against HIV-1 and HIV-2 [28]. Most of the AZT derivatives showed antiviral activity in the lower micromolar concentration range. It should be notice that all these compounds were inactive against HIV in thymidine kinase-deficient cells, pointing to the compounds' requirement to release free AZT to afford antiviral efficacy. Tumor necrosis factor-alpha, so-called TNF-?, is a cytokine produced by numerous cell types among which monocytes/macrophages play a major role [29-40]. Investigation of the biological properties of TNF-?, in vitro as well as in vivo models, has revealed that this cytokine has both beneficial and unfavourable effects. In this context, it is interesting to search for new drugs working as stimulators or inhibitors of TNF-? production. It was found that N-(adamant-1-yl)monothiophthalimide and N-(adamant-2-yl)monothiophthal-imide showed over 200% enhancing of cytokine production, while some other imides were inhibitors. The known drug bropirimine is orally active immunomodulator that stimulates production of TNF-? and other cytokines and is now under phase II clinical trials for treatment of bladder carcinoma [43]. The inspiration for us was the search for bropirimine adamantane analogues [44]. The synthesis of adamantylated pyrimidines was based on the Traube reaction of 3-(adamantan-1-yl)-3-oxopropionic acid ethyl ester with urea, thiourea, guanidine as well as acetamidine, respectively. Then the compounds obtained were converted into respective bromo-, thio- and S-alkyl derivatives. The significant anticancer and antimicrobial properties of [2-(6-adamantan-1-yl-2-methylpyrimidin-4-ylsulfanyl)ethyl]dimethylamine were found.

Słowa kluczowe

PL

adamantan; pochodne adamantanu; właściwości biologiczne

EN

adamantane derivatives; anticancer properties

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Wiadomości Chemiczne
• Rocznik: 2004
• Tom: [Z] 58, 7-8
• Strony: 599--612
• Opis fizyczny: Bibliogr. 44 poz., schem., wykr.

Twórcy

autor

Orzeszko A.

• Katedra Chemii, SGGW w Warszawie, ul. Nowoursynowska 159C, 02-787 Warszawa
• Instytut Chemii, Wojskowa Akademia Techniczna w Warszawie, ul. Kaliskiego 3, 00-908 Warszawa

Bibliografia

• [1] S. Landa, Chem. Listy, 1933,27,415.
• [2] R.C. Fort, P.R. Schleyer, Chem. Rev. 1964,64,277.
• [3] E.I. Bagrii, Adamantany, Nauka, Moskwa, 1989.
• [4] P.R Schleyer, J. Am. Chem. Soc., 1957,79,3292.
• [5] H. Stetter, O. Bander, W. Neumann, Chem. Ber., 1956,89,1922.
• [6] Z. Kazimierczuk, A. Orzeszko, Helv. Chim. Acta, 1999,82, 2020.
• [7] W.L. Davies, R.R. Grunert, R.F. Haff, J.W. McGahen, E.M. Neumayer, M. Paulshock, J.C. Watts, T.R. Wood, E.C. Hermann, C.E. Hoffmann, Science, 1964,144, 862.
• [8] A. Zajec, M. Gorczyca, Chemia leków, PZWL, Warszawa 1999.
• [9] R.S. Schwab, A.C. England, D.C. Poskanzer, R.R. Young, J. Am. Med. Assoc., 1969,208, 1168.
• [10] V.G.H. Evidente, C.H. Adler, J.N. Caviness, K. Gwinn-Hardy, Clin. Neuropharmacol., 1999, 22, 30.
• [11] K.K. Jain, Expen Opin. Invest. Drugs, 2000, 9, 1397.
• [12] S. Garoufallias, A. Vyzas, G. Fytas, G.B. Foscolos, A. Chytiroglou, Ann. Pharmaceutiques Franc., 1988,46,97.
• [13] J.-J. Wang, S.-S. Wang, C.-F. Lee, M.-A. Chung, Y.-T. Chem, Chemotheraphy, 1997,43, 182.
• [14] A. Papadaki-Valiraki, S. Papakonstantinou-Garoufalias, P. Markos, A Chytyroglou-Lada, M. Hosoya, J. Balzarini, E. De Clercq, Farmaco, 1993,48, 1091.
• [15] D. Płachta, B.J. Starościak, Acta Polon. Pharm., 1994, 51, 51.
• [16] A. Orzeszko, R. Gralewska, B.J. Starościak, Z. Kazimierczuk, Acta. Biochim. Pol., 2000, 87.
• [17] A. Orzeszko, B. Kamińska, G. Orzeszko, B.J. Starościak, Farmaco, 2000, 55, 619.
• [18] A. Orzeszko, B. Kamińska, BJ. Starościak, ibid., 2002, 57, 619.
• [19] P.S. Manchand, R.L. Cerruti, J.A. Martin, C.H. Hill, J.H. Merrett, E. Keech, R.B. Belshe, E.V. Connell, I.S. Sim, J. Med. Chem., 1990,33, 1992.
• [20] M.A. El-Sherebeny, Arch. Pharm. Pharm. Med. Chem., 2000,333, 323.
• [21] A. Da Settimo, A.M. Marini, G. Primafiore, F. Da Settimo, Farmaco, 1995, 50, 321.
• [22] G. Stamatiou, A. Kolocouris, N. Kolocouris, G. Fytas, G.B. Focolos, J. Neyts, E. De Clerq, Bioorg. Med. Chem. Lett., 2001,11, 2137.
• [23] E. De Clercq, Nature Rev., 2002,1,13.
• [24] K. Parang, L.I. Wiebe, E.E. Knaus, Curr. Med. Chem., 2000,7, 995.
• [25] N. Kolocouris, A. Kolocouris, G.B. Focolos, G. Fytas, J. Neyts, E. Padalko, J. Balzarini, R. Snoeck, G. Andrei, E. De Clerq, J. Med. Chem., 1996,39, 3307.
• [26] E. De Clerq, J. Antimicrobial Chemotherapy, 1989, 23a, 35.
• [27] E. De Clerq, Collect. Czech. Chem. Commun., 1998,63,449.
• [28] J. Balzarini, E. De Clerq, B. Kamińska, A. Orzeszko, Antiviral Chemistiy&Chemoterapy, 2003, 14, 139.
• [29] D. Mannei, C. Murray, W. Risau, M. Claus, Immunology Today, 1996,17, 254.
• [30] M. Fujita, T. Hirayama, N. Ikeda, Bioorg. Med. Chem., 2002, 10, 3113.
• [31] H. Miyachi, A. Ogasawara, A. Azuma, Y. Hashimoto, ibid., 1997, 5, 2095.
• [32] H. Miyachi, A. Azuma, A. Ogasawara, E. Uchimura, N. Watanabe, Y. Kobayashi, F. Kato, M. Kato, Y. Hashimoto, J. Med. Chem. 1997,40,2858.
• [33] K. Nishimura, Y. Hashimoto, S. Iwasaki, Chem. Pharm. Bull., 1994, 42, 1157.
• [34] Y. Shibata, M. Shichita, K. Sasaki, K. Nishimura, Y. Hashimoto, S. Iwasaki, ibid., 1995,43, 177.
• [35] K. Nishimura, Y. Hashimoto, S. Iwasaki, Biochem. Biophys. Res. Comm., 1994,199, 455.
• [36] Y. Shibata, K. Sasaki, Y. Hashimoto, S. Iwasaki, ibid., 1994, 205,1992.
• [37] G. Kaplan, Immunology 1994,191, 564.
• [38] A. Orzeszko, W. Lasek, T. Świtaj, M. Stoksik, B. Kamińska, Farmaco, 2003, 58, 371.
• [39] Z. Kazimierczuk, A. Górska, T. Świtaj, W. Lasek, Bioorg. Med. Chem. Lett., 2001, 11, 1197.
• [40] J.K. Maurin, W. Lasek, A. Gorska, T. Świtaj, M. Wamil, I. Młynarczyk, Z. Kazimierczuk, Anti-Cancer Drug Design, 2001,16, 73.
• [41] J.J. Wang, A.S. Wang, C.F. Lee, M.A. Chung, Y.T. Chem, Chemotherapy, 1997,43, 182.
• [42] JJ. Wang, Y.T. Chem, T.Y. Liu, C.W. Chi, Anti-Cancer Drug Design, 1998, 13, 779.
• [43] S. Akira, H. Hemmi, Immunol. Lett., 2003,85, 85.
• [44] B. Orzeszko, Z. Kazimierczuk, J.K. Maurin, A.E. Laudy, B.J. Starościak, J. Vilpo, L. Vilpo, J. Balzarini, A. Orzeszko, Farmaco, 2004,59, 00.