Abstract
Interest in the inhibitors of type-B monoamine oxidase has grown in recent years, due to the evidence for multiple roles of one such agent (selegiline) in the pharmacological management of neurodegenerative disorders. A set of 130 reversible and selective inhibitors of MAO-B (including tetrazole, oxadiazolone, and oxadiazinone derivatives) were taken from the literature and subjected to a three-dimensional quantitative structure–activity relationship (3D-QSAR) study, using CoMFA and GOLPE procedures. The steric and lipophilic fields, alone and in combination, provided us with informative models and satisfactory predictions (q2=0.73). The validity of these models was checked against the 3D X-ray structure of human MAO-B. Flexible docking calculations, performed by using a new approach which took advantage from QXP and GRID computational tools, showed the diverse inhibitors to interact with MAO-B in a similar binding mode, irrespective of the heterocycle characterizing them. A significant trend of correlation was observed between estimated energies of the complexes and the experimental inhibition data.
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Tripton, K.F., Cell Biochem. Funct., 4 (1986) 79
Shih, J.C., Chen, K. and Geha, R.M., J. Neural Transm., 52 (1998) 1
Grimsby, J., Lan, N., Neve, R., Chen, K. and Shih, J., J. Neurochem., 55 (1990) 1166
Bach, A.W., Lan, N.C., Johnson, D.L., Abell, C.W., Bembenek, M.E., Kwan, S.W., Seeburg, P.H. and Shih, J.C., Proc. Natl. Acad. Sci. U.S.A., 85 (1988) 4934
Geha, R.M., Rebrin, I., Chen, K. and Shih, J.C., J. Biol. Chem., 276 (2001) 9877
Kochersperger, L.M., Parker, E.L., Siciliano, M., Darlington, G.J. and Denney, R.M., J. Neurosci. Res., 16 (1986) 601
Grimsby, J., Chen, K., Wang, L.J., Lan, N.C. and Shih, J.C., Proc. Natl. Acad. Sci. U.S.A., 88 (1991) 3637
Fowler, C.J., Callingham, B.A., Mantle, T.J. and Tipton, K.F., Biochem. Pharmacol., 29 (1980) 1177
Kalir, A., Sabbagh, A. and Youdim, M.B.H., Brit. J. Pharmacol., 73 (1981) 55
Shih, J.C., Chen, K. and Geha, R.M., J. Neural Transm., 52 (1998) 1
Wouters, J., Curr. Med. Chem., 5 (1998) 137
Sandler, M., Psychol. Med., 11 (1981) 455
Foley, P., Gerlach, M., Youdim, M.B.H. and Riederer, P., Parkinsonism & Related Disorders, 6 (2000) 25
Kneubuhler, S., Thull, U., Altomare, C., Carta, V., Gaillard, P., Carrupt, P.-A., Carotti, A. and Testa, B., J. Med. Chem., 38 (1995) 3874
Altomare, C., Cellamare, S., Summo, L., Catto, M., Carotti, A., Thull, U., Carrupt, P.-A., Testa, B. and Stoeckli-Evans, H., J. Med. Chem., 41 (1998) 3812
Gnerre, C., Catto, M., Leonetti, F., Weber, P., Carrupt, P.-A., Altomare, C., Carotti, A. and Testa, B., J. Med. Chem., 43 (2000) 4747
Binda, C., Newton-Vinson, P., Hubalek, F., Edmondson, D.E. and Mattevi, A., Nat. Struct. Biol., 9 (2002) 22
Lebreton, L., Curet, O., Gueddari, S., Mazouz, F., Bernard, S., Burstein, C. and Milcent, R., J. Med. Chem., 38 (1995) 4786
Mazouz, F., Gueddari, S., Burstein, C., Mansuy, D. and Milcent, R., J. Med. Chem., 36 (1993) 1157
Mazouz, F., Lebreton, L., Milcent, R. and Burstein, C., Eur. J. Med. Chem., 25 (1990) 659
Mazouz, F., Lebreton, L., Milcent, R. and Burstein, C., Eur. J. Med. Chem., 23 (1988) 441
Bernard, S., Paillat, C., Oddos, T., Seman, M. and Milcent, R., Eur. J. Med. Chem., 30 (1995) 471
McMartin, C. and Bohacek, R.S., J. Comput. Aid.-Mol. Des., 11 (1997) 333
Goodford, P.J., J. Med. Chem., 28 (1985) 849
Stewart, J.J.P., J. Comput.-Aid. Mol. Des., 4 (1990) 1
Wouters, J., Ooms, F., Jegham, S., Koenig, J. J., George, P. and Durant, F., Eur. J. Med. Chem., 32 (1997) 721
Ferenczy, G.G., Reynolds, C.A., and Richards, W.G., Eur. J. Comp. Chem., 11 (1990) 159
Gaillard, P., Carrupt, P.-A., Testa, B. and Boudon, A., J. Comput. Aid. Mol. Des., 8 (1994) 83
Cramer, R.D. III, Patterson, D.E. and Bunce, J.D., J. Am. Chem. Soc., 110 (1988) 5959
Baroni, M., Constantino, G., Cruciani, G., Parigi, R. and Clementi, S., Quant. Struct.-Act. Relat., 12 (1993) 9
Mohamadi, F., Richards, N.G.J., Guida, W.C., Liskamp, R., Lipton, M., Caufield, C., Chang, G., Hendrickson, T. and Still, W.C., J. Comput. Chem. 11 (1990) 440
Wang, R., Lai, L. and Wang, S., J. Comput.-Aid. Mol. Des., 16 (2002) 11
Taylor, R.D., Jewsbury, P.J. and Essex, J.W., J. Comput.-Aid. Mol. Des., 16 (2002) 151
Carotti, A., Carrieri, A., Chimichi, S., Boccalini, S. M., Cosimelli, B., Gnerre, C., Carotti, A., Carrupt, P.-A., Testa, B., Bioorg. Med. Chem. Lett., 12 (2002) 3551
Geha, R.M., Chen, K. and Shih, J.C., J. Neurochem., 75 (2000) 1304
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Carrieri, A., Carotti, A., Barreca, M.L. et al. Binding models of reversible inhibitors to type-B monoamine oxidase. J Comput Aided Mol Des 16, 769–778 (2002). https://doi.org/10.1023/A:1023815426730
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DOI: https://doi.org/10.1023/A:1023815426730