Planejamento e desenvolvimento de novos derivados acridínicos, quinolínicos, indólicos e piridínicos com potencial atividade antitumoral

Abstract

A highly efficient drug that does not cause collateral damage in the treatment of varied types of cancer has been the desire of many study groups. Over the years, this has been arousing the academic interest worldwide in the search for healing or less harmful and more effective treatments. In this perspective, this work sought the development of a series of new acrylate derivatives coupled to nitrogenous nuclei with potential antitumor action, in the perspective of obtaining compounds with high potentiality and specificity. Therefore, 11 new acrylate derivatives coupled to acridine, quinolinic, indolic and pyridine nuclei have been planned and developed, 10 of which are inedited in the literature. The compounds were obtained from the condensation of different aromatic aldehydes with different reactive methylene groups through a Knovenagel type reaction in ethanolic and basic medium. Fifteen compounds were obtained, four of them intermediates (JM-01, AC-01, ACN-01 and AC-02) and 11 final compounds that presented yields of 51-86% and melting range ranging from 1 to 4 ºC, which gives a certain guarantee of the purity of the products. The structures of the obtained derivatives were elucidated by infrared-IR techniques, mass spectrometry and by 1H NMR and 13C NMR spectroscopy, showing absorption bands characteristic of the functional groupsproposed in the structures, especially the bands and signals of the common vinyl hydrogen in all compounds ranging from 5.73 to 9.30 ppm, thus proving the success of the proposed synthesis. The mass spectra corroborated with the success of the syntheses, presenting masses with expected values. The derivatives were submitted to a docking study, with scores varying from -58.8549 to -16.1303, with the best results being attributed to ICIP, ACMD, PAIP and CAIC derivatives. Interaction tests with DNA were performed by means of an evaluation of absorbance spectroscopy, observing the interaction of the compounds with the targets. In the analysis of interaction with DNA, four of them (ICIP, CAQA, CAAC and ACIP) showed interaction with DNA shifting the wavelength. Among of all derivatives, the ICIP stood out for the good results, both in the docking study, with value close to the reference drug, and with interaction with DNA, by presenting hyperchromic effect, allowing an interaction on both sides of the molecule, and also for being a inedited compound. This molecule presents itself as promising compound for the continuity of the evaluations as a drug candidate.