Solid phase organic synthesis of polyamine derivatives and initial biological evaluation of their antitumoral activity

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 6, 1998, Pages 635-640

  Tomasi, Sophie ^a   Le Roch, Myriam ^a   Renault, Jacques ^a   Corbel, Jean Charles ^a   Uriac, Philippe ^a   Carboni, Bertrand ^b   Moncoq, Damien ^c   Martin, Bénedicte ^c   Delcros, Jean Guy ^c  

^a Laboratoire de Pharmacochimie   (France)

^b UNIVERSITÉ DE RENNES 1   (France)

^c Inst de Recherche Contre le Cancer   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CALMODULIN; POLYAMINE DERIVATIVE; PUTRESCINE; PUTRESCINE DERIVATIVE; SPERMINE; SPERMINE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LEUKEMIA L 1210; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

AMINE OXIDASE (COPPER-CONTAINING); ANIMALS; ANTINEOPLASTIC AGENTS; CALMODULIN; CATTLE; CELL SURVIVAL; DEAMINATION; LEUKEMIA L1210; MODELS, CHEMICAL; OXIDATION-REDUCTION; OXIDOREDUCTASES ACTING ON CH-NH GROUP DONORS; PUTRESCINE; SPERMINE; TUMOR CELLS, CULTURED;

EID: 0032539877     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00086-9     Document Type: Article

References (33)

1. 1 Inhibition of polyamine metabolism ; Mc Cann, P.P.; Pegg, A.E.; Sjoerdsma, A. Eds.; Academic Press, San Diego, 1987. The Physiology of Polyamines; Bachrach, U.; Heimer, Y.M. Eds.; CRC Press, Boca Raton, Florida, 1989, Vol. 1 and 2. The Neuropharmacology of Polyamines; Carter C. Ed.; Academic press, San Diego, 1994. For a recent review of the various biological activities of polyamines, see : Blagbrough, I.S.; Carrington, S.; Geall, A.J. Pharm. Sci. 1997, 3, 223-233.
2. 1 Inhibition of polyamine metabolism ; Mc Cann, P.P.; Pegg, A.E.; Sjoerdsma, A. Eds.; Academic Press, San Diego, 1987. The Physiology of Polyamines; Bachrach, U.; Heimer, Y.M. Eds.; CRC Press, Boca Raton, Florida, 1989, Vol. 1 and 2. The Neuropharmacology of Polyamines; Carter C. Ed.; Academic press, San Diego, 1994. For a recent review of the various biological activities of polyamines, see : Blagbrough, I.S.; Carrington, S.; Geall, A.J. Pharm. Sci. 1997, 3, 223-233.
3. 1 Inhibition of polyamine metabolism ; Mc Cann, P.P.; Pegg, A.E.; Sjoerdsma, A. Eds.; Academic Press, San Diego, 1987. The Physiology of Polyamines; Bachrach, U.; Heimer, Y.M. Eds.; CRC Press, Boca Raton, Florida, 1989, Vol. 1 and 2. The Neuropharmacology of Polyamines; Carter C. Ed.; Academic press, San Diego, 1994. For a recent review of the various biological activities of polyamines, see : Blagbrough, I.S.; Carrington, S.; Geall, A.J. Pharm. Sci. 1997, 3, 223-233.
4. 1 Inhibition of polyamine metabolism ; Mc Cann, P.P.; Pegg, A.E.; Sjoerdsma, A. Eds.; Academic Press, San Diego, 1987. The Physiology of Polyamines; Bachrach, U.; Heimer, Y.M. Eds.; CRC Press, Boca Raton, Florida, 1989, Vol. 1 and 2. The Neuropharmacology of Polyamines; Carter C. Ed.; Academic press, San Diego, 1994. For a recent review of the various biological activities of polyamines, see : Blagbrough, I.S.; Carrington, S.; Geall, A.J. Pharm. Sci. 1997, 3, 223-233.
5. 2 Bradshaw, J.S.; Krakowiak, K.E.; Izatt, R.M. Tetrahedron 1992, 48, 4475-4515.
6. 3 Seiler, N.; Douaud, F.; Renault, J.; Delcros, J.G.; Havouis, R.; Uriac, P.; Moulinoux, J.P. Int. J Biochem. Cell Biol. 1997, in press.
7. 4 For some recent reviews, see : Früchtel, J.S.; Jung G. Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42. Thompson, L.A.; Ellman, J.A. Chem. Rev. 1996, 96, 555-600. Hermkens, P.H.H.; Ottenheijn, H.C.J.; Rees, D.C., Tetrahedron 1997, 53, 5643-5678.
8. 4 For some recent reviews, see : Früchtel, J.S.; Jung G. Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42. Thompson, L.A.; Ellman, J.A. Chem. Rev. 1996, 96, 555-600. Hermkens, P.H.H.; Ottenheijn, H.C.J.; Rees, D.C., Tetrahedron 1997, 53, 5643-5678.
9. 4 For some recent reviews, see : Früchtel, J.S.; Jung G. Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42. Thompson, L.A.; Ellman, J.A. Chem. Rev. 1996, 96, 555-600. Hermkens, P.H.H.; Ottenheijn, H.C.J.; Rees, D.C., Tetrahedron 1997, 53, 5643-5678.
10. 5 Martinez-Fresneda, P.; Carboni, B.; Vaultier, M. Synth. Comm., 1992, 665. Carboni, B.; Benalil, A.; Vaultier, M. J. Org. Chem. 1993, 58, 3736. Khoukhi, M.; Vaultier, M.; Benalil, A.;. Carboni, B. Synthesis., 1996, 483-488. Tomasi, S.; Eifler-Lima, V.L.; Le Roch, M.; Corbel, J.C.; Renault, J.; Uriac, P.; Mens, T.; Catros-Quemener, V.; Moulinoux, J.P. Pharm. Sci. 1997, 3, 241-247.
11. 5 Martinez-Fresneda, P.; Carboni, B.; Vaultier, M. Synth. Comm., 1992, 665. Carboni, B.; Benalil, A.; Vaultier, M. J. Org. Chem. 1993, 58, 3736. Khoukhi, M.; Vaultier, M.; Benalil, A.;. Carboni, B. Synthesis., 1996, 483-488. Tomasi, S.; Eifler-Lima, V.L.; Le Roch, M.; Corbel, J.C.; Renault, J.; Uriac, P.; Mens, T.; Catros-Quemener, V.; Moulinoux, J.P. Pharm. Sci. 1997, 3, 241-247.
12. 5 Martinez-Fresneda, P.; Carboni, B.; Vaultier, M. Synth. Comm., 1992, 665. Carboni, B.; Benalil, A.; Vaultier, M. J. Org. Chem. 1993, 58, 3736. Khoukhi, M.; Vaultier, M.; Benalil, A.;. Carboni, B. Synthesis., 1996, 483-488. Tomasi, S.; Eifler-Lima, V.L.; Le Roch, M.; Corbel, J.C.; Renault, J.; Uriac, P.; Mens, T.; Catros-Quemener, V.; Moulinoux, J.P. Pharm. Sci. 1997, 3, 241-247.
13. 5 Martinez-Fresneda, P.; Carboni, B.; Vaultier, M. Synth. Comm., 1992, 665. Carboni, B.; Benalil, A.; Vaultier, M. J. Org. Chem. 1993, 58, 3736. Khoukhi, M.; Vaultier, M.; Benalil, A.;. Carboni, B. Synthesis., 1996, 483-488. Tomasi, S.; Eifler-Lima, V.L.; Le Roch, M.; Corbel, J.C.; Renault, J.; Uriac, P.; Mens, T.; Catros-Quemener, V.; Moulinoux, J.P. Pharm. Sci. 1997, 3, 241-247.
14. 6 Hiroshige, M.; Hauske, J.R.; Zhou, P. J. Am. Chem. Soc. 1995, 117, 11590-11591. Marsh, I.R.; Smith, H.; Bradley, M. J. Chem. Soc., Chem. Commun., 1996, 941-942. Nash, I.A.; Bycroft, B.W.; Chan, W.C. Tetrahedron Lett. 1996, 37, 2625-2628.
15. 6 Hiroshige, M.; Hauske, J.R.; Zhou, P. J. Am. Chem. Soc. 1995, 117, 11590-11591. Marsh, I.R.; Smith, H.; Bradley, M. J. Chem. Soc., Chem. Commun., 1996, 941-942. Nash, I.A.; Bycroft, B.W.; Chan, W.C. Tetrahedron Lett. 1996, 37, 2625-2628.
16. 6 Hiroshige, M.; Hauske, J.R.; Zhou, P. J. Am. Chem. Soc. 1995, 117, 11590-11591. Marsh, I.R.; Smith, H.; Bradley, M. J. Chem. Soc., Chem. Commun., 1996, 941-942. Nash, I.A.; Bycroft, B.W.; Chan, W.C. Tetrahedron Lett. 1996, 37, 2625-2628.
17. Kellam, B.; Bycroft, B.W.; Chhabra, S. Tetrahedron Lett. 1997, 38, 4849-4852. Byk, G.; Frederic, M.; Scherman, D. Tetrahedron Lett. 1997, 38, 3219-3222. Marsh, I.R.; Bradley, M. Tetrahedron 1997, 53, 17317-17334.
18. Kellam, B.; Bycroft, B.W.; Chhabra, S. Tetrahedron Lett. 1997, 38, 4849-4852. Byk, G.; Frederic, M.; Scherman, D. Tetrahedron Lett. 1997, 38, 3219-3222. Marsh, I.R.; Bradley, M. Tetrahedron 1997, 53, 17317-17334.
19. Kellam, B.; Bycroft, B.W.; Chhabra, S. Tetrahedron Lett. 1997, 38, 4849-4852. Byk, G.; Frederic, M.; Scherman, D. Tetrahedron Lett. 1997, 38, 3219-3222. Marsh, I.R.; Bradley, M. Tetrahedron 1997, 53, 17317-17334.
20. 7 Dixit, D.M.; Leznoff, C.C. J. Chem. Soc., Chem. Comm. 1997, 798-799. Dixit, D.M.; Leznoff, C.C. Isr. J. Chem. 1978, 17, 248-252.
21. 7 Dixit, D.M.; Leznoff, C.C. J. Chem. Soc., Chem. Comm. 1997, 798-799. Dixit, D.M.; Leznoff, C.C. Isr. J. Chem. 1978, 17, 248-252.
22. 8 Dressman, B.A.; Spangle, L.A.; Kaldor, S.W. Tetrahedron Lett. 1996, 37, 937-940.
23. 9 Szardenings, A.K.; Burkoth, T.S.; Look, G.C.; Campbell, D.A. J. Org. Chem. 1996, 61, 6720-6722.
24. 3 and the solvent removed under reduced pressure. To the crude residue dissolved in ethanol (2 mL) was added at 0°C a 1.5 N ethanolic solution of HCl (1.2 equivalents). After stirring 30 mn, ethanol was evaporated and the residue was triturated in diethyl ether to yield 3-8 and 15 as white solids which were collected and dried under reduced pressure.-for spermine derivatives 10-14 : the filtrate was concentrated to dryness under reduced pressure. The residue was triturated in diethyl ether to yield 10-14 as white solids which were collected and dried under reduced pressure. Compounds 10-15 were purified by preparative high-voltage paper electrophoresis on a PHEROGRAPH model 64 using Whatman 3MM paper with a 3% HCOOH solution.
25. 11 Rauter, H.; Di Domenico, R.; Menta, E.; Oliva, A.; Qu, Y.; Farrell, N. Inorg. Chem. 1997, 36, 3919-3927.
26. 12 Bernard, T.; Pocard, J.A.; Perroud, B.; Le Rudulier, D. Arch. Microbiol. 1986,143, 359-364.
27. 13 Delcros, J.G.; Vaultier, M.; Le Roch, N.; Havouis, R.; Moulinoux, J.P.; Seiler, N. Anticancer Drug Design 1997, 12, 35-48.
28. 14 Purified bovine serum oxidase (generous gift of Pr B. Mondovi, University La sapienza, Rome, Italy) was used for the determination of the substrate properties of the compounds. Hydrogen peroxide formation was determined at 10 μM of each compound using the horseradish peroxidase-catalyzed oxidation of homovanillic acid into a fluorescent product, following a published procedure (Snyder, S.H.; Hendley, E.D. J. Pharmacol. Exp. Ther. 1968, 163, 386-392).
29. 15 Seiler, N. in Neuropharmacology of polyamines" Carter, C. Ed., Harcourt Brace & Company, London, 1994, 1-36.
30. 2 at 37°C. The metabolic activity of cells was determined in 96 well plates (Becton Dickinson, Oxnard, CA, USA) (initial density 2500 cells/well) by formazan formation from 3-[4,5-dimethyl-thiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) (see : Mosmann, T. J. Immunol. Methods 1983, 65, 55-63).
31. 2+ (Sigma P-0134) (see ref 3).
32. 14C]putrescine (0.5 μCi; 10μM) and the desired concentrations of the test compound (final volume : 600 μL). Blank samples were run in parallel at 4°C. Uptake of putrescine was stopped by layering the cell suspension on top of a mixture of corn oil + dibutylphthalate (3+1) and centrifugation at 15000 g for 1min. The cell pellet was dissolved in 1N NaOH. Aliquots of the pellet were also used for radioactivity measurement and protein determination using the Lowry method (Pöch, N. Naunyn-Schmiedebergs Arch. Pharmacol. 1971, 268, 272-299.
33. 19 Chang, B.K.; Libby, P.R.; Bergeron, R.J.; Porter, C.W. Biochem. Biophys. Res. Commun. 1988, 157, 264-270.