Details

Autor(en) / Beteiligte

• Michelotti, Paula
• Gonçalves, Débora F.
• Duarte, Tâmie
• Sarturi, Joelma M.
• Da Silva, Rafael S.
• Rodrigues, Oscar E. D.
• Rocha, João B. T.
• Dalla Corte, Cristiane L.

Titel

Toxicological evaluation of zidovudine and novel chalcogen derivatives in Drosophila melanogaster

Ist Teil von

• Journal of biochemical and molecular toxicology, 2023-07, Vol.37 (7), p.e23356-n/a

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 μM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno‐phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p‐methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates. Highlights The toxicity of novel AZT chalcogen derivatives was investigated. AZT decreases mitochondrial oxygen flux in the OXPHOS stage in D.melanogaster. Derivatives 7A, 7D, 7M, and 7G were less toxic than AZT at the mitochondrial level. Derivative containing p‐methoxyl group is more toxic to mitochondria than AZT.