Department of Biological Sciences, College of Pharmacy, Univ Estadual Paulista, Araraquara, São Paulo, Brazil.
PLoS One. 2013 May 28;8(5):e64242. doi: 10.1371/journal.pone.0064242. Print 2013.
Rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class form part of a 6-month regimen that is ineffective against MDR and XDR TB, and incompatible with many antiretroviral drugs. Investments in R&D strategies have increased substantially in the last decades. However, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. Ruthenium complexes (SCAR) have been tested in our laboratory and showed promising activity against Mycobacterium tuberculosis. These complexes showed up to 150 times higher activity against MTB than its organic molecule without the metal (free ligand), with low cytotoxicity and high selectivity. In this study, promising results inspired us to seek a better understanding of the biological activity of these complexes. The in vitro biological results obtained with the SCAR compounds were extremely promising, comparable to or better than those for first-line drugs and drugs in development. Moreover, SCAR 1 and 4, which presented low acute toxicity, were assessed by Ames test, and results demonstrated absence of mutagenicity.
利福平是 50 多年前发现的，是第一个用于治疗结核病的新型抗生素。该类药物是 6 个月治疗方案的一部分，对耐多药和广泛耐药结核病无效，也与许多抗逆转录病毒药物不兼容。在过去几十年中，研发策略的投资大幅增加。然而，全球药物监管机构批准的新药数量并没有相应增加。钌配合物（SCAR）已在我们的实验室中进行了测试，对结核分枝杆菌表现出有希望的活性。这些配合物对 MTB 的活性比其不含金属的有机分子（游离配体）高 150 倍，细胞毒性低，选择性高。在这项研究中，有希望的结果促使我们寻求更好地了解这些配合物的生物学活性。SCAR 化合物的体外生物学结果非常有希望，与一线药物和正在开发的药物相当或更好。此外，急性毒性较低的 SCAR1 和 SCAR4 通过 Ames 试验进行了评估，结果表明没有致突变性。
