Maria de Lourdes Gonçalves Ferreira

RECENT ADVANCES IN THE SYNTHESIS OF PYRROLES

.......................................................................... INTRODUCTION ........ 413 I. ADVANCES IN THE CLASSICAL METHODS ...................................................................... . 4 14 .................................. 414 1. Knorr Pyrrole Synthesis .............................................. 2. Paal-Knorr Pyrrole Synthesis ......................................................... 3. Hantzsch Pyrrole Synthesis and Related Reactions ................................................... 11. ZAV’YALOV PYRROLE SYNTHESIS ........ 111. BARTON-ZARD PYRROLE SYNTHESIS AND RELATED REACTIONS ..................... 425 IV. PYRROLES FROM l93-DICARBONYL COMPOUNDS .................. ............ 429 V. MULTIPLE-COMPONENT REACTIONS ............................................................... 432 VI. SYNTHESES OF PYRROLES FROM ALKYNYL COMPOUNDS ................................... 436 W. OTHER REACTIONS ....................................................................... VIII. CONCLUSION ..... ...................................................................... REFERENCES ........................................ ................................................................. 446

Heterociclos 1,2,3-triazólicos: histórico, métodos de preparação, aplicações e atividades farmacológicas

The 1,2,3-triazole, known since the end of 19th century, is a very widely used heterocyclic system present in many synthetic substances and commercial pharmaceutical compounds. In fact, 1,2,3-triazoles show several applications in many areas especially as medicines against many diseases like cancer, AIDS, Parkinson and Alzheimer. Nowadays there is a large variety of known methods to obtain these heterocyclic compounds comprising mainly three synthetic routes. Nevertheless, there is no article that gives an objective overview of the synthetic methods for obtaining these kinds of azoheterocycles. This paper presents a brief history of this class of compounds, and a synthetic discussion concerning the main synthetic methods for its preparation, such as cyclization through hydrazones, concerted cycloadditon [2+3] and pseudopericyclic cyclization - and some others of restricted application, but also important. Finally, this paper also provides a brief overview on pharmacological applications of some 1,2,3-triazoles.

New carbohydrate-based chiral auxiliaries in Diels–Alder reaction

Abstract The carbohydrate derivatives 1 – 5 were evaluated as chiral auxiliaries in the Diels–Alder reaction of its acrylate derivatives 6a – e with cyclopentadiene promoted by Lewis acids. Although excellent endo : exo ratios (98:2) were obtained in many cases, the π-facial selectivities were from low to moderate (up to 60% d.e.). An effect of non-coordinating solvents reversing the stereoselectivities of adducts obtained from acrylates 6a , b was also found.

Qualidade diagnóstica da biópsia com agulha Super-core II® de nódulos mamários de cadelas

The core needle biopsy is an easy method and fast that offers tumors sample, widely used in diagnosis of mammary injuries in women. The aim of the study was the diagnostic evaluation of the biopsy in 26 mammary nodes of 19 female dogs, using the cut needle Super-core II® 14-ga x 9cm. After the biopsy, the patients had been submitted to mastectomy for attainment of mammary nodes. The biopsies specimens and the nodes had been histological analyzed and classified neoplasm according to World Health Organization (WHO). The core needle biopsy showed sensitivity of 100% and specificity of 71.4% in the diagnosis of adenocarcinomas and in the diagnosis of carcinosarcomas, the 71.4% of sensitivity and 100% of specificity. And according to Goodman and Kruskall (P<0.0001) test presented diagnostic effectiveness of 81.6%. The biopsy with Super-core II is an efficient method for the histological classification of mammary nodes in female dogs.

Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with mammary tumours and histopathological analyses

The canine BRCA2 is a tumor supressor gene which encodes the BRCA2 protein, involved in DNA repair through interaction with the RAD51 recombinase. This process is mediated by eigth BRC repeats that are encoded by BRCA2 exon 11. Two variants corresponding to human mutations in human BRC3 repeat have been reported in canine BRC3 repeat. In addition, other variants have also been described in canine BRCA2 exon 11. Considering the importance of polymorphisms in human BRCA2 to breast cancer development, this study aimed to investigate the frequency of variants in BRCA2 exon 11 in 48 blood and tissue DNA samples from bitches with canine mammary tumors (CMT), as well as, to analyze tumor stage and histopathological features. Seven Single Nucleotide Polymorphisms (SNPs) were identified, three of which were evaluated as possibily or probably deleterious variant. Interestingly, almost all the 22 mammary tumors (except one) which presented a clinical staging equal to or greater than III carried at least one mutant allele of these three variants. Besides that, no statistically significant correlation was observed between any of the reported SNPs in heterozygosis or homozygosis and either dogs data (such as breed, age or disease stage) or mammary tumors histopathological characteristics. A total of 97.9% of bitches had one to three polymorphisms of the seven identified in this study, which suggests a possibly correlation between the canine BRCA2 exon 11 polymorphisms and mammary carcinogenesis.

TP53 gene expression levels and tumor aggressiveness in canine mammary carcinomas

The protein p53 is considered to be one of the most important tumor suppressor factors. Despite this importance, a potential association between TP53 messenger (m)RNA levels and tumor aggressiveness has not been well defined in animal cancer. We assessed and correlated TP53 gene expression in 40 canine mammary carcinomas with histologic grade, tumor size, and aggressiveness. The tumors were subjected to histologic analysis and the TP53 mRNA levels determined by RT-rtPCR. Statistical analysis revealed no correlation between levels of TP53 mRNA and tumor aggressiveness (r = 0.00) or tumor growth (r = 0.06). Histologic grades (r = 0.17) and mitosis count (r = 0.12) showed a weak correlation with TP53 mRNA expression levels. These findings are consistent with molecular studies that revealed heterogeneous expression of TP53 in canine and human mammary tumors. Hence, TP53 gene expression alone cannot be considered a marker for tumor aggressiveness in canine mammary carcinomas.