R. Maccari et al. / Bioorg. Med. Chem. Lett. 21 (2011) 200–203
10. Tammali, R.; Ramana, K. V.; Srivastava, S. K. Cancer Lett. 2007, 252, 299.
203
effectiveness and, in addition, the structure–activity relationships
relevant to 5-arylidene-4-thiazolidinone ARIs were further refined.
In particular, it was observed that the replacement of the carbonyl
group in position 2 of the 2,4-thiazolidinedione scaffold with the
bioisoster thiocarbonyl group can improve inhibitory efficacy in
most of the tested compounds. Further studies will be needed to
confirm the proposed hypotheses which could rationalize this gain
in potency. Moreover, out of the tested 2-thioxo-4-thiazolidinones,
two N-unsubstituted analogues (4b and 4c) were found to be more
active than sorbinil. As observed for 2,4-TZDs, the insertion of an
acetic chain on N-3 significantly enhanced potency, thus leading
to derivatives 3b–e with in vitro efficacy very similar to that of
the structural analogue epalrestat, the only ARI currently used in
therapy.
11. Alexiou, P.; Pegklidou, K.; Chatzopoulou, M.; Nicolaou, I.; Demopoulos, V. J.
Curr. Med. Chem. 2009, 16, 734.
12. Ramana, K. V.; Srivastava, S. K. Int. J. Biochem. Cell Biol. 2010, 42, 17.
13. Costantino, L.; Rastelli, G.; Cignarella, G.; Vianello, P.; Barlocco, D. Exp. Opin.
Ther. Patents 1997, 7, 843.
14. Miyamoto, S. Chem. Biol. Inform. J. 2002, 2, 74.
15. Suzen, S.; Buyukbingol, E. Curr. Med. Chem. 2003, 10, 1329.
16. Urzhumtsev, A.; Tête-Favier, F.; Mitschler, A.; Barbanton, J.; Barth, P.;
Urzhumtseva, L.; Biellmann, J. F.; Podjarny, A.; Moras, D. Structure 1997, 5, 601.
17. El-Kabbani, O.; Wilson, D. K.; Petrash, J. M.; Quiocho, F. A. Mol. Vis. 1998, 4, 19.
18. Howard, E. I.; Sanishvili, R.; Cachau, R. E.; Mitschler, A.; Chevrier, B.; Barth, P.;
Lamour, V.; Van Zandt, M.; Sibley, E.; Bon, C.; Moras, D.; Schneider, T. R.;
Joachimiak, A.; Podjarny, A. Proteins 2004, 55, 792.
19. Sotriffer, C. A.; Krämer, O.; Klebe, G. Proteins 2004, 56, 52.
20. Costantino, L.; Rastelli, G.; Vianello, P.; Cignarella, G.; Barlocco, D. Med. Res. Rev.
1999, 19, 3.
21. Kikkawa, R.; Hatanaka, I.; Yasuda, H.; Kobayashi, N.; Shigeta, Y.; Terashima, H.;
Morimura, T.; Tsuboshima, M. Diabetologia 1983, 24, 290.
22. Terashima, H.; Hama, K.; Yamamoto, R.; Tsuboshima, M.; Kikkawa, R.;
Hatanaka, I.; Shigeta, Y. J. Pharmacol. Exp. Ther. 1984, 229, 226.
23. Ramirez, M. A.; Borja, N. L. Pharmacotherapy 2008, 28, 646.
24. Hotta, N.; Kawamori, R.; Atsumi, Y.; Baba, M.; Kishikawa, H.; Nakamura, J.;
Oikawa, S.; Yamada, N.; Yasuda, H.; Shigeta, Y. Diabetes Med. 2008, 25, 818.
25. Fresneau, P.; Cussac, M.; Morand, J.; Szymonski, B.; Tranqui, D.; Leclerc, G. J.
Med. Chem. 1998, 41, 4706.
Acknowledgements
This work was supported by University of Messina and Univer-
sity of Pisa. We are indebted to Dr. G. Pasqualetti and Dr. R. Di
Sacco (veterinary staff of Consorzio Macelli S. Miniato, Pisa) for
their valuable cooperation in bovine lens collection.
26. Maccari, R.; Ottanà, R.; Curinga, C.; Vigorita, M. G.; Rakowitz, D.; Steindl, T.;
Langer, T. Bioorg. Med. Chem. 2005, 13, 2809.
27. Maccari, R.; Ottanà, R.; Ciurleo, R.; Vigorita, M. G.; Rakowitz, D.; Steindl, T.;
Langer, T. Bioorg. Med. Chem. Lett. 2007, 17, 3886.
28. Maccari, R.; Ottanà, R.; Ciurleo, R.; Rakowitz, D.; Matuszczak, B.; Laggner, C.;
Langer, T. Bioorg. Med. Chem. 2008, 16, 5840.
Supplementary data
Supplementary data associated with this article can be found, in
29. Bruno, G.; Costantino, L.; Curinga, C.; Maccari, R.; Monforte, F.; Nicolò, F.;
Ottanà, R.; Vigorita, M. G. Bioorg. Med. Chem. 2002, 10, 1077.
30. Maccari, R.; Ciurleo, R.; Giglio, M.; Cappiello, M.; Moschini, R.; Del Corso, A.;
Mura, U.; Ottanà, R. Bioorg. Med. Chem. 2010, 18, 4049.
32. Bue-Valleskey, J. M.; Hunden, D. C.; Jones, C. D.; Panetta, J. A.; Shaw, W. N. U.S.
1996, US 5523314.
33. Kaarsholm, N. C.; Madsen, P.; Schlein, M.; Olsen, H. B.; Havelund, S.;
Steensgaard, D. B.; Ludvigsen, S.; Jakobsen, P.; Petersen, A. K.; Schluckebier,
G. PCT Int. Appl. WO 2004056347, 2004.
34. Russell, A. J.; Westwood, I. M.; Crawford, M. H. J.; Robinson, J.; Kawamura, A.;
Redfield, C.; Laurieri, N.; Lowe, E. D.; Davies, S. G.; Sim, E. Bioorg. Med. Chem.
2009, 17, 905.
35. Del Corso, A.; Barsacchi, D.; Giannessi, M.; Tozzi, M. G.; Camici, M.; Houben, J.
L.; Zandomeneghi, M.; Mura, U. Arch. Biochem. Biophys. 1990, 283, 512.
36. Values calculated by means of the freely accessible web tool Marvin Calculator
polarizability values of compounds 1–4 are available in the Supplementary
data.
References and notes
1. Kador, P. F. Med. Res. Rev. 1988, 8, 325.
2. Yabe-Nishimura, C. Pharmacol. Rev. 1998, 50, 21.
3. Brownlee, M. Nature 2001, 414, 813.
4. Ramana, K. V.; Friedrich, B.; Srivastava, S.; Bhatnagar, A.; Srivastava, S. K.
Diabetes 2004, 53, 2910.
5. Srivastava, S. K.; Ramana, K. V.; Bhatnagar, A. Endocr. Rev. 2005, 26, 380.
6. Gleissner, C. A.; Galkina, E.; Nadler, J. L.; Ley, K. Drug Discovery Today Dis. Mech.
2007, 4, 131.
7. Turner, R. C.; Holman, R. R.; Cull, C. A.; Stratton, I. M.; Matthews, D. R.; Frighi,
V.; Manley, S. E.; Neil, A.; McElroy, H.; Wright, D.; Kohner, E.; Fox, C.; Hadden,
D.UK Prospective Diabetes Study (UKPDS) Group Lancet 1998, 352, 837.
8. Zozulinska, D.; Wierusz-Wysocka, B. Diabetes Res. Clin. Pract. 2006, 74S, S12.
9. Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Diabetes Care 2004, 27, 1047.