Summary
Experimental and theoretical physico-chemical methods were used to investigate the interaction between aryl-oxazolidinones and monoamine oxidase (MAO). Several arguments suggest that these compounds interact with the flavin adenine dinucleotide (FAD) cofactor of MAO. The calculation using ab initio molecular orbital methods of the electronic properties of flavin and befloxatone, a reversible inhibitor of MAO A, led to a description of the interaction between aryl-oxazolidinones and the cofactor of the enzyme. Structure activity relationship results revealed additional sites of interaction with the protein core of MAO A.
As a resust of this work, a model is proposed for the reversible inhibition of MAO by oxazolidinones via long distance, reversible interactions with the FAD cofactor of the enzyme.
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References
Baudoux G, Vercauteren DP (1989) CPS, a contour plotting system. Facultés Universitaire Notre-Dame de la Paix, Namur.
Chin S, Vercauteren DP, Luken WL, Re M, Scateni R, Tagliavini R, Vanderveken DJ, Baudoux G (1989) Modem techniques in computational chemistry. MOTECC 89. ESCOM, Leiden, pp 499–546.
Ferrey G, Rovei V, Strolin Benedetti M, Gomeni C, Languillat J (1985) Antidepressant activity of toloxatone, a selective MAO-A inhibitor, in depressed patients. In: Borrows CD, Norman TR, Dennerstein L (eds) Clinical and pharmacological studies in psychiatric disorders. Libbey, Paris, pp 83–86.
Frisch MJ, Binkley JS, Schlegel HB, Raghavachari K, Melius C, Martin R, Stewart JJ, Bobrowicz FW, Rohlfing CM, Kahn LR, Defrees DJ, Seeger R, Whiteside RA, Fox DJ, Fleuder EM, Pople JA (1988) GAUSSIAN 86 Canegie-Mellon Quantum Chemistry Publishing Unit, Pittsburgh.
Hinde RJ, Luken WL, Chin S (1988) IBM Kingston Technical Report KGN-141, June 20th, Kingston.
Johnson CK (1971) Program ORTEP II. Oak Ridge Thermal Ellipsoid Plot, ORNL-3794 UC-4-Chemistry, Oak Ridge, Tennessee.
Koenig JJ, Moureau F, Vercauteren D, Durant F, Ducrey F, Jarreau FX (1992) Befloxatone, a spontaneously reversible MAO-A inhibitor: modélisation at molecular level. Clin Neuropharmacol 15: 424B.
Moureau F, Wouters J, Vercauteren DP, Collin S, Evrard G, Durant F, Ducrey F, Koenig JJ, Jarreau FX (1992) A reversible monoamine oxidase inhibitor, toloxatone: structural and electronic properties. Eur J Med Chem 27: 939–948.
Pople JA (1977) In: Schaefer HF (ed) Applications of electronic structure theory. Modern technical chemistry series, vol 4. Plenum, New York, p 1.
Rovei V, Thomas J, Koenig JJ, Jarreau FX (1992) Befloxatone, a new oxazolidinone reversible MAO-A inhibitor. Clin Neuropharmacol 15: 425A.
Scarbrough FE, Shieh HS, Voet D (1977) The X-Ray crystal structure of the molecular complex bis(lumiflavin-2,6-diamie-9-ethylpurine)-ethanol-water. Acta Crystallogr B33: 2512–2523.
Sheldrick GM (1976) SHELX76. A program for crystal structure determination. University of Cambridge, Cambridge.
Sheldrick GM (1986) SHELX86. A program for crystal structure determination. Institute of Anorganic Chemistry, University of Göttingen.
Silverman RB (1988) Mechanism-based enzyme inactivation. Chemistry and enzymology vol 1, 2. CRC Press, Boca Raton.
Steward JM, Machin PA, Dickinson CW, Ammon HL, Heck M, Flack H (1976) XRAY76, Technical report TR-445. Computer Science Center, University of Maryland, Maryland.
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© 1994 Springer-Verlag
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Wouters, J. et al. (1994). Experimental and theoretical study of reversible monoamine oxidase inhibitors: structural approach of the active site of the enzyme. In: Tipton, K.F., Youdim, M.B.H., Barwell, C.J., Callingham, B.A., Lyles, G.A. (eds) Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission, vol 41. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9324-2_41
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DOI: https://doi.org/10.1007/978-3-7091-9324-2_41
Publisher Name: Springer, Vienna
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