ABSTRACT
A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths (n = 1-3). ß-Dimethyl and α-methyl derivatives were also synthesised. The compounds were tested as melatonin agonists and antagonists using the pigment aggregation of Xenopus melanophores as the biological assay. A number of these compounds were potent melatonin agonists, the potency depending on the length of the alkyl chain, the orientation of the methoxy and fluorine substituents, the amide chain length and, for the ethyl side-chain analogues, the presence of ß-substituents.
ABSTRACT
Cancer is a disease of genomic instability, a multistep process involving numerous mutations and chromosomal aberrations. Telomeres are highly specialized structures at the ends of chromosomes and function to stabilize and protect the ends of linear chromosomes, therefore determining cellular immortalization. Homeostasis of telomere length is a multifactor-dependent process. Since cellular immortalization is an early and essential step towards cancer, the aim of the present study was to determine immortalization genes that are significant in colon cancer and assess their usefulness in the early diagnosis of this tumor. Expression profiles of 119 transcripts known to be involved in cellular immortalization were assessed with oligonucleotide microarrays in 13 probes of colon adenocarcinoma (low and high clinical stages) and 9 probes of controls (normal colon tissue) and were compared among these groups with the use of the Significant Analysis Microarray (SAM) software and independently verified with the effect size parameter. Eighteen genes with significantly differential expression between high clinical stage colon cancer and the control group, and 21 with differential expression between low clinical stage colon cancer and the control group were identified. Nine genes showing altered expression in both low and high clinical stage colon cancer: ACD (TPP1), DKC1 and ERCC1, MYC, MAX, NBN, NOLA2, PRKDC and HSP82 should, in particular, be the subjects of further studies including QRT-PCR methods.
