Planejamento, síntese e avaliação farmacológica de novas antraquinonas, tetraidropirimidinas e N-acilidrazonas

Abstract

The present work explored, in a first part, the synthesis of novel anthraquinones and tetrahydropirimidines, potential imunossupressive agents. In a second chapter was realized a synthesis of the N-acylhidrazones amino acids derivatives. The first part of chapter 1 consisted of synthesis and imunosupressive evaluation of the 1,4-diamineanthraquinone and 1,4-dihydroxyanthraquinone derivatives. For this, ten substances were synthesized; two derivatives of 1,4-diamineanthraquinone and 7 derivatives of 1,4-dihydroxyanthraquinone, in moderate to satisfactory yields (31-90%). Substances 12, 13, 15, 16, 19 and 22-26 were submitted to in vitro evaluation of inhibition of NO production in the Laboratory of Immunology from UFJF. The results showed that diamine 12 had better imunosupressive activity, being able to inhibit 92.6% of NO production. Substances 13 and 22 were evaluated under the model of experimental autoimmune encephalomyelitis (EAE), in which was observed improvement in clinical signs of the mice disease that were treated with these substances. The second part of chapter 1 consisted of the synthesis and immunosuppressive evaluation of 5 tetrahydropirimidines that were unpublished, they were obtained by reaction of ethionamide with N-alkyl diamines. The test results of inhibition of NO production of substances 31a, 31d and 31e were not significant due to cytotoxicity presented in cell viability tests. As part of the doctor stage held in Farmanguinhos/Fiocruz, chapter 2 of this work consisted of the synthesis and antituberculous evaluation of new N-acylhydrazones (48a-q), amino acid derivatives, obtained in moderate to satisfactory yields (25-84%). These substances were tested for antibacterial activity against M. tuberculosis in IPEC-Fiocruz/RJ. The evaluation results showed the importance of the 5- nitrofuranyl and Cbz for the activity, and the phenylalanine derivative 48c is the most active with MIC of 12.5 mg / mL.