Evaluation of intermolecular interactions in thioxanthone derivatives: substituent effect on crystal diversity

A family of 9H-thioxanthen-9-one derivatives and two precursors, 2-[(4-bromophenyl) sulfanyl]-5-nitrobenzoic acid and 2-[(4-aminophenyl) sulfanyl]-5-nitrobenzoic acid, were synthesized and studied in order to assess the role of the different substituent groups in determining the supramolecular motifs. From our results we can conclude that Etter's rules are obeyed: whenever present the -COOH head to head strong hydrogen bonding dimer, R-2(2)(8) synthon, prevails as the dominant interaction. As for -NH2, the best donor when present also follows the expected hierarchy, an NH center dot center dot center dot O(COOH) was formed in the acid precursor (2) and an NH center dot center dot center dot O(C=O) in the thioxanthone (4). The main role played by weaker hydrogen bonds such as CH center dot center dot center dot O, and other intermolecular interactions, pi-pi and Br center dot center dot center dot O, as well as the geometric restraints of packing patterns shows the energetic interplay governing crystal packing. A common feature is the relation between the p-p stacking and the unit cell dimensions. A new synthon notation, R`, introduced in this paper, refers to the possibility of accounting for intra- and intermolecular interactions into recognizable and recurring aggregate patterns.

Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

Tert Hypermethylated Oncologic Region (THOR) como um biomarcador para cancro

O cancro é uma das principais causas de morte relacionada com doença, sendo responsável por cerca de 14 milhões de novos casos e 8,2 milhões de mortes em todo o mundo. Os tipos de cancro mais comuns são o cancro do pulmão, mama, colorretal e da próstata, sendo o cancro do pulmão, colorretal e da mama os mais mortais. Embora cada tipo de cancro apresente alterações únicas que são adquiridas durante a carcinogénese, biomarcadores universais de malignidade e métodos para estabelecer a progressão da doença em diferentes neoplasias não existem e continuam a ser um grande desafio em oncologia clínica. Uma característica do cancro é a manutenção dos telómeros, a qual é crucial para a autorrenovação de todos os tumores malignos. A ativação da telomerase ocorre através da expressão da transcriptase reversa humana (hTERT) e tem sido relatado que a sua expressão aumenta marcadamente na invasão tumoral. O mecanismo de regulação da hTERT não está completamente elucidado; no entanto, tem sido relatado que a hipermetilação de ilhas CpG apresenta um papel essencial na expressão da hTERT em células cancerígenas telomerase-positivas. O nosso grupo recentemente identificou uma região específica no promotor da hTERT (denominada THOR) que está hipermetilada e associada com a ativação da telomerase em tecido cancerígeno. THOR foi capaz de prever a progressão do tumor e evolução clínica do paciente em diversos tumores pediátricos e adultos. Objetivo do estudo - Pretendemos investigar se a metilação do THOR pode ser um biomarcador de doença maligna e de evolução clínica do paciente em diferentes cancros adultos.