SupraSelen Laboratory, Department of Chemistry, Federal University Fluminense, Institute of Chemistry, Campus do Valonguinho, 24020-141, Niterói-RJ, Brazil.
Department of Chemistry, Federal University of Santa Catarina- Campus Florianopolis, Trindade, Florianopolis, SC, 88040-900, Brazil.
Eur J Med Chem. 2022 Dec 5;243:114687. doi: 10.1016/j.ejmech.2022.114687. Epub 2022 Aug 18.
Chagas Disease is caused by the protozoan Trypanosoma cruzi and is considered a tropical neglected disease by the World Health Organization (WHO). The main drugs used in the therapy of the disease are obsolete and, as a result, it still kills millions of people every year. Therefore, the development of new drugs is urgent, as is the research reported in this article, in which new triazole selenides were synthesized through a simple methodology and to evaluate their potential against T. cruzi, through a combination of in vitro and in silico assays. With the combination of two molecular scaffolds already known for this activity, sixteen new hybrid compounds were obtained, showing yields ranging from 40 to 90%, and their biological potentials were tested. Two of the evaluated hybrids showed potent trypanocidal activity (11m and 11n), comparable to the positive control benznidazole. Density functional theory (DFT) studies were correlated with cyclic voltammetry assays to investigate the LUMO energy, which demonstrated a correlation with the observed trypanocidal activity. These results are promising, considering 11m and 11n as hit compounds in the development of new antichagasic drugs.
克氏锥虫病由原生动物克氏锥虫引起，被世界卫生组织（WHO）视为热带被忽视疾病。该病的主要治疗药物已经过时，因此每年仍有数百万人因此病死亡。因此，开发新药迫在眉睫，正如本文所报道的研究一样，通过一种简单的方法合成了新的三唑硒化合物，并通过体外和计算结合评估它们对克氏锥虫的潜在作用。通过将两种已知具有这种活性的分子支架组合，获得了十六种新的杂化化合物，产率范围为 40%至 90%，并对其生物潜力进行了测试。两种评估的杂种化合物表现出很强的杀锥虫活性（11m 和 11n），与阳性对照苯并硝唑相当。密度泛函理论（DFT）研究与循环伏安法测定相关联，以研究最低未占分子轨道能量，该能量与观察到的杀锥虫活性相关。考虑到 11m 和 11n 是开发新型抗恰加斯病药物的有效化合物，这些结果很有希望。
