Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate.

Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.

The 1,3-dipolar cycloaddition reaction in the functionalization of carbon nanofibers.

Carbon nanofibers were functionalized using a reaction scheme described in the literature for 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the condensation of an alpha-amino acid and an aldehyde. The reagents used were Z-Gly-OH and paraformaldehyde. Their reaction with carbon nanofibers was studied as a solid mixture by controlled heating in the DSC. An oxazolidinone intermediate was formed as the major product. Z-Gly-OH and paraformaldehyde were also reacted with a model compound (anthracene) in DMF solution leading to the formation of a considerable amount of anthraquinone. These studies suggested that, under the conditions investigated, the 1,3-dipolar cycloaddition reaction was not favoured, and the main result of functionalization was the formation of quinone-type groups as a consequence of an oxidation process.

Functionalization of carbon nanofibers by a Diels-Alder addition reaction.

This paper reports functionalization of CNF via a Diels-Alder addition reaction and the characterization of the obtained materials. The functionalization was assessed by a calorimetric technique (DSC) and the morphology of CNF modified materials was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The functionalization was observed to be dependent on the preparative conditions. Detailed analysis of the CNF modified material surface using TEM, shows a deposited layer homogeneously distributed over the CNF structures with an average thickness of about 15 nm. Finally the chemical activity of the raw CNF and functionalized CNF was analyzed to determine the pH of the point of zero charge (pHpzc) values. The results obtained showed that the functionalized CNF materials presented enhanced acid activity comparatively with the modified carbonaceous materials reported in literature.

Novel structurally similar chromene derivatives with opposing effects on p53 and apoptosis mechanisms in colorectal HCT116 cancer cells.

In the present work, novel chromene derivatives fused with the imidazo[1,2-a]pyridine nucleus were tested for their anticancer potential in the human colorectal cancer HCT116 cells. Compounds 2a and 2c showed significant growth inhibitory activity with GI50 of 15 µM and 11 µM, respectively. Compound 2c, the most potent, has a carbamate group in position 8 of the pyridine ring, and showed significant cell cycle arrest and induction of cell death by apoptosis, even at 5 µM. Besides different potencies, chromene analogs 2a and 2c showed different mechanisms of action. Whereas the carbamate-free chromene 2a induced cell cycle arrest at G1/G0 phase, compound 2c showed to arrest cell cycle at both S and G2 phases. Chromene derivative 2a at concentrations higher than its GI50 remarkably induced caspases-dependent apoptosis in a p53-independent manner. On the other hand, compound 2c increased significantly p53 levels and induced apoptosis in a p53- and caspases-dependent manner, even at concentrations lower than its GI50. Both compounds increased the Bax/Bcl-2 ratio, induced mitochondria depolarization and activated MAP kinases. In conclusion, two novel and structurally similar chromene derivatives showed cytotoxicity to HCT16 cells through opposing effects on p53 levels and apoptosis mechanisms, which may be relevant for further development of drugs acting on distinct molecular targets useful in the treatment of cancers with different genetic profiles and for personalized medicine.

The reactions of diaminomaleonitrile with isocyanates and either aldehydes or ketones revisited.

A reinvestigation of the reactions of urea derivatives of diaminomaleonitrile 2 with aldehydes or ketones in the presence of triethylamine has established that the products of these reactions are not pyrimidino[5,4-d]pyrimidines 9 as previously reported, but 8-oxo-6-carboxamido-1,2-dihydropurines 12, which are oxidized rapidly in air to the corresponding 6-carboxamidopurines 13. Similarly, the reaction of Schiff base derivatives of DAMN 5 with isocyanates in the presence of triethylamine gives the substituted 2-oxoimidazoles 20 and not the pyrimidine derivatives 8 as previously claimed. The compounds 20 cyclize in solution and are easily oxidized to 8-oxopurine-6-carbonitriles 22, which give the same 8-oxopurine-6-carboxamides 13 upon further hydrolysis.