Safety profile of azt derivatives : phenylseleno moieties confer different cytotoxic responses in fresh human erythrocytes during in vitro exposures

The cellular effects of three molecules based on antiretroviral zidovudine (AZT) on erythrocytes viability and functionality was proposed and investigated in this in vitro study. A short-term treatment was conducted to estimate the effects of AZT and selenium-containing derivatives (10500μM) on membrane damage, redox disturbance and thiol containing enzymes activity in freshly human erythrocytes. The effects of derivatives towards erythrocytes differed considerably. Overall, derivative 3 (methylphenylseleno) had similar patterns to prototypal AZT, showing no significant signals of cytotoxicity. The insertion of either chlorophenylseleno or, in a certain way, phenylseleno portions in the structure of AZT molecule was detrimental to erythrocytes and this effect seems to involve a pro-oxidant activity and disruption in thiol balance. This was not true for the derivative encompassing methylphenylseleno portion, making it a promising candidate for in vivo studies. Authorization: Authorized by the UFSM Ethics Committee under the number (0089.0.243.000-07).