SÍNTESE, ELUCIDAÇÃO ESTRUTURAL, AVALIAÇÃOO ANTITUMORAL E ANTIFÚNGICA DE QUINOLINONAS DERIVADAS DE CHALCONAS SULFONAMIDAS

Abstract

Few studies describe the synthesis, the application of 1-4 quinolinones, as well as the study of its structural properties. Such compounds can be quite useful in therapy, since several biological activities have been reported for quinolinones. The present work describes the synthesis, structural elucidation by crystallography, antitumor and antifungal evaluation of ten unpublished quinolinones. The quinolinones were obtained by the reaction between chalcone sulfonamides and benzaldehydes substituted in positions 2, 3 and 4 by F, Cl and NO2. The compounds were synthesized in a single reaction step from intermediate chalcones. The products precipitated essentially pure and were isolated by simple filtration. The reaction yield was between 32 and 70%. The structure of the compounds was confirmed and characterized by IV, 1H and 13C NMR, HMBC, melting point and structural elucidation by crystallography. The crystallographic study has been shown to be extremely important to decipher the molecular arrangement, whose technique assists areas such as pharmacology, pharmacognosy and pharmacodynamics. The data obtained by monocrystal X-ray diffraction allowed the evaluation of geometric parameters, interatomic distances and angles, intermolecular interactions, supramolecular arrangement, Hirshfiel surface and Fingerprints. The molecules crystallized in the monoclinic, orthorhombic and triclinic systems, their interatomic distances, as well as connection angles were measured and compared with structures previously deposited in a CCDC database. The intermolecular interactions responsible for packaging the ten compounds obtained were weak non-classical hydrogen interactions and only the compound (E) –3 - (2- nitrobenzylidene) -2- (4-methoxyphenyl) -2,3-dihydro-1- ( phenylsulfonyl) quinolin 4 (1H) -one, presented hydrophobic interaction of type π ∙∙∙ π. The greatest contribution of the supramolecular arrangement occurred through the O ∙∙∙ H contacts, mainly in compounds that have nitro group in one of the ligands. Then, when considering that the potential for tumor and fungicidal inhibition of quinolinone-type compounds has been extensively studied and that many studies have shown satisfactory results, in vitro antitumor evaluation was carried out on three melanoma, colon and nervous system tumor cell lines. center at the Drug Development Center of the Federal University of Ceará (NPDM-UFC). The antifungal evaluation against strains of Candida sp was carried out at the Bioprospecting Laboratory for Antimicrobial Molecules at UFC (LABIMAN-UGC). All the synthesized compounds did not show antitumor activity against the strains used in this work; however, they did show antifungal activity. The antifungal activity of the synthesized quinolinones was in the concentration range of 33 - 132µg.mL-1 , against isolates of fluconazole-resistant C. albicans, probably due the presence of substituints on the fenil group of the quinoline, however, they did not show antifungal activity against C. parapsilosis (ATCC ® 22019 ™).