Síntese e avaliação biológica de derivados de 6-mercaptopurina, carboidratos e aminoálcoois

Abstract

The doctoral thesis entitled Synthesis and Biological Evaluation of Derivatives of 6-Mercaptopurine, Carbohydrates and Aminoalcohol is presented in three chapters that describe the synthesis and characterization of compounds with potential antiparasitic activity (Leishmania, Plasmodium berghei), antibacterial (bacteria Gram positive and negative, Mycobacterium tuberculosis) and peritoneal macrophages of mammals. 53 compounds were obtained in this work, with 30 firsts, namely: Chapter 1 was described in the synthesis of compounds 27, 14 novel derivatives of 6-mercaptopurine (6MP), was described in Chapter 2 the synthesis of compounds 14, 6 being derived from unpublished 1 D-glucose and derived novel D-ribonolactona, was described in Chapter 3 the synthesis of compounds 14, 9 amino unpublished. The first chapter shows the synthesis of derivatives of 6-MP containing 1,2,3triazole derivatives and steroids. The triazole derivatives of 6-MP were obtained by a reaction of type 1,3-dipolar cycloaddition "click" using a terminal alkyne and an azide group. Derivatives of 6-MP containing steroids, without the spacer triazole, was obtained through a nucleophilic substitution reaction between the salt of 6-MP and mesylates cholic acid and deoxycholic acid. Among the compounds subjected to biological evaluation, derivatives of 6-MP in conjunction with steroids showed better activity in Leishmania and most showed a significant activity in P. berghei. No compound tested showed cytotoxicity in vitro for mouse peritoneal macrophages to g / mL.µthe maximum concentration of 48 µg/mL. The second chapter shows the synthesis and characterization of D-glucose derivatives containing 1,2,3-triazole, obtained by reaction type "click" derivatives of Dgliconolactona and D-ribonolactona. Although the compounds tested did not show effective antibacterial and antiparasitic activity, showed no toxicity to mammalian macrophages. The third chapter describes the synthesis and characterization of aromatic amino derivatives with varied chain length and chemical function and had significant biological activity, especially in L. Major. The structures of the products obtained were elucidated by their spectra in the infrared, 1H NMR and 13C, homonuclear COSY contour map, melting point and mass spectra with high resolution.