Síntese e atividades antioxidante e antitumoral de 5´-arilseleno azidotimidina

Abstract

The synthesis of compounds that use a nucleoside as the base structure, has an intense field application. Among these compounds, the most known nowadays is azydothymidine or zidovudine, a drug which was first synthesized to work against tumor processes. However, it was discovered that it could take action to viral combat and now it is the drug of choice in the treatment of acquired immunodeficiency syndrome (AIDS). On the other hand, organochalcogens compounds have been calling the attention of the scientific community, mainly because of their potential in biological molecules containing these atoms. Considering this last factor and aiming to explore the structural basis of nucleosides and biological influences that changes in the 5' position of the deoxyribose ring of AZT would promote, it was planned through an efficient and accessible synthetic route to produce a new series of nucleosides, the 5'-arylseleno azidothymidine, which had the insertion of the selenium atom connected to different aril groups. Moreover, the series of selenium derivatives were evaluated for their toxicological potential for oxidative stress (TBARS and thiol peroxidase), where the compounds 5´-p-methylseleno azidothymidine 3b and 5´-p-chloroseleno azidothymidine (3h) had the results of this series, with potential as antioxidant agent. After this, the compounds 3b and 3h were tested against culture cell lines of bladder cancer (5637). The tests aimed to assess the cytotoxicity, cell morphology, apoptosis analysis and gene expression. The results showed that the compounds 3b and 3h present apoptotic profile, additionally they seem to modulate the expression of anti-apoptotic gene. The results obtained indicate that the compounds 3b and 3h in addition of presenting an antioxidant potential, have a pro-apoptotic profile, even more effective than AZT itself. Considering all the results presented, it was concluded that this new nucleoside serie has great antitumor potential and can be used as a chemopreventive, combined to the antioxidant potential.