RESUMO
Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON's multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types.
RESUMO
We investigated the specificity of glycosyltransferases toward donor substrates in two complementary directions. First we prepared simple N-acetyl-alpha-D-glucosamine 1-diphosphates: methyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-diphosphate, benzyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-diphosphate, 4-phenylbutyl-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-diphosphate, by the coupling of the corresponding activated alkyl phosphates with N-acetyl-alpha-D-glucosamine 1-phosphate. These diphosphates as well as 2-acetamido-2-deoxy-alpha-D-glucopyranose 1-diphosphate, tested as donors of N-acetylglucosamine in a reaction catalyzed by Neisseria meningitidis N-acetylglucosaminyltransferase (LgtA), proved to be devoid of activity. Evaluated as inhibitors, only 2-acetamido-2-deoxy-alpha-D-glucopyranose 1-diphosphate showed some inhibitory activity with an IC50 value of 7 mM. In the second approach, we prepared sugar nucleotide mimics having the diphosphate bridge replaced by the oxycarbonylaminosulfonyl linker. The surrogate of GDP-Fuc was synthesized as a 9:1 alpha/beta anomeric mixture, in 40% yield, starting from chlorosulfonyl isocyanate, perbenzylated l-fucopyranose, and a guanosine derivative, protected on the exocyclic amine and secondary hydroxyl functions of ribose. Then two deprotection steps, hydrogenolysis and enzymatic hydrolysis catalyzed by penicillin G amidase afforded the target molecule to be tested as fucose donor with recombinant human alpha-(1-->3/4)-fucosyltransferase (FucT-III). Tested as a 4:1 alpha/beta anomeric mixture, both in the absence and in the presence of cationic cofactors, this new guanosine fucose conjugate proved to be ineffective. Its inhibitory activity toward FucT-III evaluated through a competition fluorescence assay was very poor (IC50 value of 20 mM). The surrogate of UDP-GlcNAc that was already known as its protected acetylated derivative, tested as N-acetylglucosamine donor with LgtA in the presence of Mn(2+) turned out not to be active either.
