RESUMO
We have performed: (i) conformational analysis of two novel cytotoxic C2-substituted pyrrolo[2,3-f]quinolines 5e and 5g in deuterated dimethylsulfoxide (DMSO-d(6)) utilizing NOE results from NMR spectroscopy; (ii) molecular dynamics (MD) calculations in water, DMSO and dimyristoyl phosphatidylcholine bilayers and (iii) molecular docking and MD calculations on DNA nucleotide sequences. The obtained results for the two similar in structure molecules showed differences in: (i) their conformational properties in silico and in media that reasonably simulate the biological environment; (ii) the way they are incorporated into the lipid bilayers and therefore their diffusion ability and (iii) molecular docking capacity as it is depicted from their different binding scores.
Assuntos
Dimetil Sulfóxido/química , Bicamadas Lipídicas/química , Pirróis/química , Quinolinas/química , Domínio Catalítico , Difusão , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular , Soluções , Solventes/química , Água/químicaRESUMO
An investigation of the controlled release profile of mono-layered formulations of the hormone melatonin in modified aqueous media is described. The tablets used were comprised of hydroxypropylmethylcellulose (HPMC K15M) and sodium alginate with melatonin (fully soluble in the dioctyl sulfosuccinate (DSS) containing simulated intestinal solution). Three different sets of tablets (diameters 7.5, 10.0 and 13.0 mm) were tested with respect to the influence of their sizes on the hormone's release; the general trend observed was that tablets with larger surface area values had lower % release. A decrease in the value of W(o), obtained from the ratio [H(2)O]/[DSS], results to the predominance of DSS conformers in the aqueous media, which are less likely to solubilize melatonin effectively.
Assuntos
Alginatos/química , Ácido Dioctil Sulfossuccínico/química , Melatonina/administração & dosagem , Metilcelulose/análogos & derivados , Tensoativos/química , Água/química , Preparações de Ação Retardada , Portadores de Fármacos , Composição de Medicamentos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio , Derivados da Hipromelose , Cinética , Melatonina/química , Metilcelulose/química , Tamanho da Partícula , Solubilidade , Propriedades de Superfície , ComprimidosRESUMO
In view of the variable oral absorption, short biological half-life and extensive first pass metabolism of the pineal hormone melatonin, an investigation of its solubilization profile in modified aqueous media is described. Four readily available surfactants were examined with respect to their ability to enhance the solubility of melatonin under simulated physiological conditions. The most effective surfactant was found to be the sodium salt of dioctyl sulfosuccinate (DSS), which augmented the aqueous solubility of the hormone by 23%. This is attributed to a favourable stereoelectronic interaction between DSS and the nucleus of melatonin, which seems to be independent of the pH of the dissolution medium. A noteworthy synergistic effect in the aqueous solubilization of the hormone occurs when a 1:2 DSS-sodium dodecyl sulphate mixture is used.
