Síntese, caracterização da N-(4- azidobutil) Ftalimida, estudo in silico e bioensaio de toxicidade frente às larvas de Artemia salina Leach.

Abstract

Since ancient times, humanity has been searching for relief and cures for diseases, inducing in-depth studies in the search for molecules with biological properties. In this sense, drug research and development (R&D) is a highly relevant process for the pharmaceutical industry and has been evolving technologically, primarily with the help of computational tools. However, even with all this technological advancement, society faces challenges such as microbial resistance to the therapeutic array available on the market, necessitating R&D into new therapeutic alternatives. In this scenario, two classes of compounds that have been attracting interest from the scientific community are organic azides and phthalimides, which exhibit numerous biological activities. In this sense, the objective of this work was to synthesize N-(4-azidobutyl)phthalimide, evaluate its pharmacokinetic and pharmacodynamic properties with the aid of in silico tools, and investigate its toxicological potential using Artemia salina Leach. N-(4-azidobutyl)phthalimide was obtained through a bimolecular nucleophilic substitution reaction in the form of a yellow solid with a yield of 89.38%. In the in silico analysis, N-(4-azidobutyl)phthalimide demonstrated good oral bioavailability, since it did not violate any of the rules established by Lipinski. Furthermore, the azide demonstrated the ability to act as an enzyme inhibitor, scoring positively in the Molinspiration online property calculation. The in silico toxicological test did not reveal any toxic effects of phthalimide. Based on this premise, a bioassay was performed with Artemia salina. However, in this test, the azide presented an LC50 of 425 μg/mL, falling within the range of 500 and 1000 μg/mL, thus characterizing a mildly toxic substance. In summary, phthalimide azide was obtained with an excellent yield of 89.38% and presented a good oral bioavailability profile, as well as a good toxicological profile according to the in silico analysis and mildly toxic activity in the acute toxicity bioassay using Artemia salina.