Solid-phase synthesis of a combinatorial library of dihydroceramide analogues and its activity in human alveolar epithelial cells

Bioorganic and Medicinal Chemistry

Volumn 15, Issue 1, 2007, Pages 50-62

  Villorbina, Gemma ^a   Canals, Daniel ^a   Carde, Lydia ^a,b   Grijalvo, Santiago ^a,b   Pascual, Rosalia ^c   Rabal, Obdulia ^c   Teixidó, Jordi ^c   Fabriàs, Gemma ^a   Llebaria, Amadeu ^a   Casas, Josefina ^a   Delgado, Antonio ^a,b  

^a DEPARTMENT OF ENVIRONMENTAL CHEMISTRY   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

^c INSTITUT QUÍMIC DE SARRIÀ   (Spain)

Author keywords

Analogues; Apoptosis; Ceramide; Combinatorial; COPD; Dihydroceramide; Solid phase; Sphingolipid

Indexed keywords

CERAMIDE DERIVATIVE; DIHYDROCERAMIDE DERIVATIVE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL GROWTH; COMBINATORIAL LIBRARY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIASTEREOISOMER; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LUNG ALVEOLUS EPITHELIUM; RESPIRATORY TRACT DISEASE; SOLID;

APOPTOSIS; BINDING SITES; CELL CYCLE; CELL LINE; CELL PROLIFERATION; CERAMIDES; COMBINATORIAL CHEMISTRY TECHNIQUES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; EPITHELIAL CELLS; FLOW CYTOMETRY; HUMANS; MOLECULAR STRUCTURE; PULMONARY ALVEOLI; SENSITIVITY AND SPECIFICITY; STEREOISOMERISM;

EID: 33750942863     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2006.10.024     Document Type: Article

References (47)

1. Hannun Y.A. Science 274 (1996) 1855-1859
2. Liao J.Y., Tao J.H., Lin G.Q., and Liu D.G. Tetrahedron 61 (2005) 4715-4733
3. Brodesser S., Sawatzki P., and Kolter T. Eur. J. Org. Chem. (2003) 2021-2034
4. Jayadev S., Liu B., Bielawska A.E., Lee J.Y., Nazaire F., Pushkareva M., Obeid L.M., and Hannun Y.A. J. Biol. Chem. 270 (1995) 2047-2052
5. Obeid L.M., Linardic C.M., Karolak L.A., and Hannun Y.A. Science 259 (1993) 1769-1771
6. Demedts I.K., Demoor T., Bracke K.R., Joos G.F., and Brusselle G.G. Respir. Res. 7 (2006) 53
7. Petrache I., Natarajan V., Zhen L., Medler T.R., Richter A.T., Cho C., Hubbard W.C., Berdyshev E.V., and Tuder R.M. Nat. Med. 11 (2005) 491-498
8. Bielawska A., Crane H.M., Liotta D., Obeid L.M., and Hannun Y.A. J. Biol. Chem. 268 (1993) 26226-26232
9. Bose R., Verheij M., Haimovitz-Friedman A., Scotto K., Fuks Z., and Kolesnick R. Cell 82 (1995) 405-414
10. Ogretmen B., Schady D., Usta J., Wood R., Kraveka J.M., Luberto C., Birbes H., Hannun Y.A., and Obeid L.M. J. Biol. Chem. 276 (2001) 24901-24910
11. Jiang Q., Wong J., Fyrst H., Saba J.D., and Ames B.N. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 17825-17830
12. Tserng K.Y., and Griffin R.L. Biochem. J. 380 (2004) 715-722
13. For a related example of a solid-phase synthesis of a Cer library, see:. Park J., Li Q., Chang Y.T., and Kim T.S. Bioorg. Med. Chem. 13 (2005) 2589-2595
14. Chang Y.T., Choi J., Ding S., Prieschl E.E., Baumruker T., Lee J.M., Chung S.K., and Schultz P.G. J. Am. Chem. Soc. 124 (2002) 1856-1857
15. Fukano Y., Oishi M., Chibana F., Numazawa S., and Yoshida T. J. Toxicol. Sci. 31 (2006) 99-109
16. Higashimoto Y., Yamagata Y., Iwata T., Ishiguchi T., Okada M., Masuda M., Satoh H., and Itoh H. Respiration 72 (2005) 629-635
17. Mata M., Sarria B., Buenestado A., Cortijo J., Cerda M., and Morcillo E.J. Thorax 60 (2005) 144-152
18. Thompson L.A., and Ellman J.A. Tetrahedron Lett. 35 (1994) 9333-9336
19. Bunin B.A. The Combinatorial Index (1998), Academic Press, London
20. 2/EtOH), as described in: Wallace, O. B. Tetrahedron Lett. 1997, 38, 4939-4942. (see also Experimental).
21. MOE (Molecular Operating Environment); Chemical Computer Group Inc: 1010 Sherbrroke West. Suite 910, Montreal, H3A 2R7, 2004.03 Release.
22. Pascual R., Borrell J.I., and Teixido J. Mol. Divers. 6 (2003) 121-133
23. Retrospectively, the diversity of this smaller full-array was assessed in the new accessible chemical space resulting from the combination of the modified reactant lists: 12 Grignard reagents (allylmagnesium bromide not included) and 22 acyl chlorides (benzoyl chloride instead of trifluoroacetyl chloride). This virtual library of 264 compounds (12 × 22) was characterized with the same set of descriptors (see text) and subsequently processed by PCA. As stated above, diversity was measured by cell-based methods in terms of both space and population coverage. In order to prevent cluster artifacts in the comparison, space was again partitioned in 36 clusters using the HRC-complete method. For this retrospective evaluation of the synthesized combinatorial library, we took as reference the best simulated annealing optimized 5 × 6 full-array selection carried out in the space defined by the 264-membered virtual library. Hence, the synthesized subset represents up to 60% of population coverage (44% space coverage), compared to the maximum full-array optimal value found of 71% (67% space). We finally performed a second PRALINS run to find how to complement, when needed, our synthesized combinatorial library in order to reach a degree of coverage closer to the maximum value. Thus, the optimal 6 × 6 sub-library forcing the selection of the 5 × 6 synthesized subset is found to include pentylmagnesium bromide, now yielding 71% of the population coverage (53% space).
24. Hoffman R.V., Maslouh N., and Cervantes-Lee F. J. Org. Chem. 67 (2002) 1045-1056
25. 2 = (1:1, isocratic), flow rate: 1 mL/min; erythro: 42.3 min; threo: 45.1 min.
26. Chung S.K., and Lee J.M. Tetrahedron: Asymmetry 10 (1999) 1441-1444
27. Dondoni A., Perrone D., and Turturici E. J. Org. Chem. 64 (1999) 5557-5564
28. Chun J., He L., Byun H.S., and Bittman R. J. Org. Chem. 65 (2000) 7634-7640
29. Gordeev M.F., Luehr G.W., Hui H.C., Gordon E.M., and Patel D.V. Tetrahedron 54 (1998) 15879-15890
30. Reactions were monitored by cleavage of the resin (see Ref. 20) and HPLC or HPLC-MS analysis. Reaction yields were estimated on the basis of the loading of the starting resins (see Experimental for details).
31. Kaiser E., Colescot R., Bossinge C., and Cook P. Anal. Biochem. 34 (1970) 595-596
32. The analysis was complicated by the fact that two different sets of N,O(1) and N,O(3)-diacylated adducts were identified in the crude mixture. Acylation at C1(OH) can be interpreted as a result of a O-acyl migration in the course of the cleavage step of the initially formed N,O(3)-diacylated adduct.
33. Raith K., Darius J., and Neubert R.H.H. J. Chromatogr. A 876 (2000) 229-233
34. Unpublished results from our laboratory.
35. Dagan A., Wang C., Fibach E., and Gatt S. Biochem. Biophys. Acta 1633 (2003) 161-169
36. Ogretmen B., Pettus B.J., Rossi M.J., Wood R., Usta J., Szulc Z., Bielawska A., Obeid L.M., and Hannun Y.A. J. Biol. Chem. 277 (2002) 12960-12969
37. Calculated using the CLogP algorithm incorporated in ChemDraw Ultra (9.0.1), licensed from BioByte Corp (http://www.biobyte.com).
38. 1 group of the sphingoid base (see Fig. 2).
39. Lavrentiadou S.N., Chan C., Kawcak T., Ravid T., Tsaba A., van der Vliet A., Rasooly R., and Goldkorn T. Am. J. Respir. Cell Mol. Biol. 25 (2001) 676-684
40. Lin C.F., Chen C.L., Chang W.T., Jan M.S., Hsu L.J., Wu R.H., Fang Y.T., Tang M.J., Chang W.C., and Lin Y.S. J. Biol. Chem. 280 (2005) 23758-23765
41. Shikata K., Niiro H., Azuma H., Tachibana T., and Ogino K. Bioorg. Med. Chem. Lett. 13 (2003) 613-616
42. Johnson C.R., Chun J., Bittman R., and Jarvis W.D. J. Pharmacol. Exp. Ther. 309 (2004) 452-461
43. Stiban J., Fistere D., and Colombini M. Apoptosis 11 (2006) 773-780
44. Siskind L.J., Kolesnick R.N., and Colombini M. J. Biol. Chem. 277 (2002) 26796-26803
45. Venkataraman K., and Futerman A.H. Biochim. Biophys. Acta 1530 (2001) 219-223
46. Dragusin M., Gurgui C., Schwarzmann G., Hoernschemeyer J., and van Echten-Deckert G. J. Lipid Res. 44 (2003) 1772-1779
47. Leonard J., Lygo B., and Procter G. Advanced practical organic chemistry. second ed. (1995), Blackie Academic & Professional