Eugenol ß-Amino/ß-Alkoxy Alcohols with Selective Anticancer Activity.

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol ß-amino alcohol and ß-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three ß-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Antitumour and Toxicity Evaluation of a Ru(II)-Cyclopentadienyl Complex in a Prostate Cancer Model by Imaging Tools.

BACKGROUND: Ruthenium complexes have been extensively investigated for their prospective value as alternatives to cisplatin. Recently, we reported the in vitro anticancer properties of a family of organometallic ruthenium( II)-cyclopentadienyl complexes and have explored their mechanism of action. OBJECTIVE: The purpose of this study was to evaluate the in vivo antitumour efficacy and toxicity of one of these Ru(II) compounds, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO2] (TM85) which displayed an interesting spectrum of activity against several cancer cells. METHODS: Studies to assess the antitumour activity and toxicity were performed in a metastatic prostate (PC3) mice model using ICP-MS, nuclear microscopy, elemental analysis and Transmission Electron Microscopy (TEM). RESULTS: TM85 showed low systemic toxicity but no significant tumour reduction, when administered at tolerated dose (20mg/kg) over 10 days. Ru was mainly retained in the liver and less in kidneys, with low accumulation in tumour. Increased bilirubin levels, anomalous Ca and Fe concentrations in liver and mitochondria alterations were indicative of liver injury. The hepatotoxicity observed was less severe than that of cisplatin and no nephrotoxicity was found. CONCLUSION: Under the experimental conditions of this study, TM85 is less toxic than cisplatin, induces similar tumour reduction and avoids the formation of metastatic foci. No renal toxicity was observed by the analysis of creatinine levels and the effective renal plasma flow by 99mTc-MAG3 clearance. Hence, it can be considered a valuable compound for further studies in the field of Ru-based anticancer drugs.

Does the simultaneous tumor necrosis factor receptor 2, tumor necrosis factor promoter gene polymorphism represent a higher risk for alcoholic liver disease?

BACKGROUND AND AIM: Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that seems to play a crucial role in the pathogenesis of alcoholic liver disease (ALD). TNF-alpha exerts its effects by binding to specific receptors (TNFR); the polymorphism of TNFRII T587G has been associated with increased TNF apoptotic response and its presence may increase the risk to develop liver disease. The aim of this study was to evaluate the prevalence of the TNF-alpha G238A promoter and TNFRII polymorphisms, individually or simultaneously, in ALD. METHODS: TNF-alpha G238A and TNFRII T587G polymorphisms were studied in 103 unrelated patients with ALD (biopsy confirmed or clinical evidence) and in 76 heavy drinkers without liver disease (NLD). Single nucleotide polymorphism gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms method. All patients had, at least, a 5 year history of alcohol consumption greater than 80 g/day. RESULTS: TNF-alpha G238A allele frequency was similar in both groups. TNFRII T587G allele frequency was slightly higher in the ALD group than in the NLD group (21 vs. 18%, P=NS). TNF-alpha G238A and TNFRII T587G were simultaneously present in six ALD patients and in none of NLD patients (P=0.04). CONCLUSION: Although individually there was no association between TNFRII T587G or TNF-alpha G238A polymorphisms and ALD, this study suggests that the presence of both polymorphisms may enhance the susceptibility for ALD. TNF-alpha G238A may increase TNF-alpha production, which when associated with TNFRII T587G, can further exacerbate TNF-alpha response leading to a greater risk of ALD.