Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells.

The present study aimed to investigate the effect of AZT derivates containing tellurium (Te) on human breast cancer cell lines and the mechanisms underlying cell death. The inhibitory effect of AZT and its derivatives (7m and 7r) was determined by the MTT assay (6.25, 12.5, 25, 50 and 100 µM in 24 and 48 h time points), meanwhile the induction of apoptosis and the cell cycle phases was investigated by flow cytometry. The MTT assay showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 12.5 µM, while commercial AZT showed low antitumor potential. In flow cytometric analysis, we demonstrate that the AZT derivatives do not induce apoptosis at the concentration tested and promote the cell cycle arrest in the S phase. Besides, predicted absorption, distribution, metabolization, excretion and toxicity analysis suggest that the compounds possess a good pharmacokinetic profile and possibly less toxicity when compared to conventional AZT. These compounds containing tellurium in their formulation are potential therapeutic agents for breast cancer.

Selenothymidine protects against biochemical and behavioral alterations induced by ICV-STZ model of dementia in mice.

The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection received a bilateral dose of STZ [11.3 µmol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE.

Contribution of dopaminergic and adenosinergic systems in the antinociceptive effect of p-chloro-selenosteroid.

This study investigated the antinociceptive action of p-chloro-selenosteroid (PCS), administered by intragastric route (i.g.) to mice against acute models. The contribution of adenosinergic, dopaminergic, serotonergic, nitric oxide and opioid systems was investigated. It was evaluated if the administration of PCS triggers toxic effect. Treatment with PCS (10mg/kg) reduced writhing induced by acetic acid and its effect lasts up to 48 h after treatment. The compound caused an inhibition in neurogenic and inflammatory phases of nociception and in paw edema induced by formalin. The licking behavior triggered by glutamate was reduced by PCS. In the tail-immersion test, PCS elicited an increase in delta latency response. Pretreatment with caffeine (3mg/kg, intraperitoneally [i.p.]) and SCH58261 (3mg/kg, i.p.), antagonist at adenosinergic receptors, SCH23390 (0.05 mg/kg, i.p.) and sulpiride (5mg/kg, i.p.), antagonist at dopaminergic receptors, caused a reduction in the antinociceptive action of PCS in the glutamate test. By contrast, pretreatment with WAY100635 (0.7 mg/kg, i.p.), ketanserin (0.3mg/kg, i.p.), ondasentron (0.5mg/kg, i.p.), l-arginine (600 mg/kg, i.p.) and naloxone (1mg/kg, subcutaneous [s.c.]) did not abolish the antinociceptive effect caused by PCS (10mg/kg, i.g.) administration. The animals treated with PCS did not show alterations in locomotor and exploratory activities, in biochemical parameters evaluated, food and water consumption, as well as in the body weight. These results clearly showed the antinociceptive action of PCS in different animal models without causing acute toxic effects in mice. Adenosinergic and dopaminergic systems seem to be related to the mechanisms by which PCS elicits antinociception.