DFT calculation of four new potential agents muscarinic of bispyridinium type: structure, synthesis, biological activity, hydration, and relations with the potents W84 and DUO-3O

Journal of Computer-Aided Molecular Design - Tập 25 - Trang 145-161 - 2010
M. Alcolea Palafox1, P. Posada-Moreno2, A. L. Villarino-Marín2, C. Martinez-Rincon2, I. Ortuño-Soriano2, I. Zaragoza-García2
1Departamento de Química-Física I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain
2Departamento de Enfermería, Escuela de Enfermería, Universidad Complutense, Madrid, Spain

Tóm tắt

Four new potential agents muscarinic (allosteric modulators) were synthesized and studied by using the B3LYP density functional method. The optimum conformation and geometry structure of these compounds were determined and analyzed. Solvent effects were considered including a variable number (1–15) of explicit water molecules surrounding the compound in order to simulate the first hydration shell, as well as using the Tomasi’s polarized continuum model (PCM). A similar simultaneous analysis of the potents W84 and DUO-3O allosteric modulator of muscarinic receptors was also carried out. The effect of the hydration on the total atomic charges and several intermolecular distances of interest were also discussed. The biological activity against acetylcholine of our four synthesized bispyridinium salts was determined. Relationships/tendencies structure–activity were established. Several general conclusions were underlined.

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