Pelargonium sidoides is an important traditional medicine in South Africa with a well-defined history of both traditional and documented use of an aqueous-ethanolic formulation of the roots of P. sidoides (EPs 7630), which is successfully employed for the treatment of respiratory tract infections. There is also historical evidence of use in the treatment of tuberculosis. The aim of this study was to develop a platform of Mycobacterium tuberculosis (Mtb) kinase enzymes that may be used for the identification of therapeutically relevant ethnobotanical extracts that will allow drug target identification, as well as the subsequent isolation of the active compounds. Mtb kinases, Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase were cloned, produced in Escherichia coli and characterized. HPLC-based assays were used to determine the enzyme activities and subsequently the inhibitory potentials of varying concentrations of a P. sidoides extract against the produced enzymes. The enzyme activity assays indicated that these enzymes were active at low ATP concentrations. The 50% inhibitory concentration (IC50) of an aqueous root extract of P. sidoides against the kinases indicated SK has an IC50 of 1.2 μg/ml and GK 1.4 μg/ml. These enzyme targets were further assessed for compound identification from the P. sidoides literature. This study suggests P. sidoides is potentially a source of anti-tubercular compounds and the Mtb kinase platform has significant potential as a tool for the subsequent screening of P. sidoides extracts and plant extracts in general, for compound identification and elaboration by selected extract target inhibitor profiling.

中文翻译：

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用于验证天竺葵（天竺葵科）抗结核活性的新型激酶平台

Pelargonium sidoides 是南非的一种重要传统药物，在传统和有记载的使用 P. sidoides 根 (EPs 7630) 的水乙醇制剂方面有着明确的历史，该制剂已成功用于治疗呼吸道感染。也有用于治疗结核病的历史证据。本研究的目的是开发一个结核分枝杆菌 (Mtb) 激酶平台，该平台可用于鉴定治疗相关的民族植物提取物，以识别药物靶点，以及随后分离活性化合物。克隆了 Mtb 激酶、核苷二磷酸激酶、高丝氨酸激酶、乙酸激酶、甘油激酶、硫胺素单磷酸激酶、核糖激酶、天冬​​氨酸激酶和莽草酸激酶，在大肠杆菌中产生并表征。基于 HPLC 的测定用于确定酶活性，随后确定不同浓度的 P. sidoides 提取物对产生的酶的抑制潜力。酶活性测定表明这些酶在低 ATP 浓度下是有活性的。P. sidoides 水根提取物对激酶的 50% 抑制浓度 (IC50) 表明 SK 的 IC50 为 1.2 μg/ml，GK 为 1.4 μg/ml。从 P. sidoides 文献中进一步评估这些酶靶点以鉴定化合物。这项研究表明 P. sidoides 是抗结核化合物的潜在来源，并且 Mtb 激酶平台具有作为后续筛选 P. sidoides 提取物和一般植物提取物的工具的巨大潜力，