Crystallographic study of candidates for prototypes of new drugs Nacylhydrazones derivatives

The crystal structure determination plays an important role in the development of candidates for new drugs N-acylidrazonic because it provides information for a better understanding of the pharmacodynamic and physicochemical properties of them. In this work, we determined the crystal structure of the compounds LASSBio-1834, LASSBio-1835, LASSBio-1860 and LASSBio-1366 with X-ray powder diffraction data (DRXP). These compounds were planned and synthesized at the Laboratory of Evaluation and Synthesis of Bioactive Substances - LASSBio® of the Federal University of Rio de Janeiro (UFRJ). LASSBio-1834, LASSBio-1835 and LASSBio-1860 are N-acylhydrazonic derivatives phosphodiesterase type 4 (PDE4) inhibitors and adenosine A2A receptor ligands, in vitro, designed as candidates for vasodilator prototypes. The LASSBio-1366 is a N-methyl-Nacylhydrazonic derivative PDE4 inhibitor and tumor necrosis factor alpha (TNF-α), in vitro, and also active in models of induced inflammation by lipopolysaccharide (LPS), in vivo, thus, it may be highlighted as an anti-inflammatory prototype. Topas Academic and DASH softwares were applied to determine the crystal structure, later the Rietveld method was used to refine them. The results of determination of the crystalline structure showed structural aspects of the solid phase of the compounds allowing the characterization of the relative configuration E of the double bond imine for all the compounds. We identified for the first time 1,5-N … S σ-hole intramolecular interactions in the candidates for prototypes of new drug of LASSBio® and the molecular modeling corroborated the results obtained in the DRXP. We verified how changes in the chemical structure of the compounds affected: the properties of the compounds with the differential scanning calorimetry technique and the morphology with scanning electron microscopy and morphological prediction of the crystal. (author)