Novel kinase platform for the validation of the anti-tubercular activities of Pelargonium sidoides (Geraniaceae)

BMC Biotechnology

R. L. Roth¹  C. P. Kenyon²  N. Tshililo³  L. Mbabala³  M. J. B. Dewar⁴  S. W. Odeyemi⁴  V. Lukman⁵  N. M. Vlok⁶ 

[1] Council for Scientific and Industrial Research, Pretoria, South Africa;Council for Scientific and Industrial Research, Pretoria, South Africa;DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, 7505, Cape Town, South Africa;DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, 7505, Cape Town, South Africa;Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, 1709, Johannesburg, South Africa;Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, 1709, Johannesburg, South Africa;Council for Scientific and Industrial Research, Pretoria, South Africa;Proteomics Spectrometry Unit, Central Analytical Facility, University of Stellenbosch, Private Bag X1, Matieland, 7600, Stellenbsoch, South Africa;

关键词: Mycobacterium tuberculosis;    Kinases;    Anti-tubercular;    Target identification;   

DOI  :  10.1186/s12896-020-00643-w

来源: Springer

【 摘 要 】

BackgroundPelargonium 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.ResultsMtb 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.ConclusionThis 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.

【 授权许可】

CC BY