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Abstract Title:

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

Abstract Source:

BMC Biotechnol. 2020 09 29 ;20(1):50. Epub 2020 Sep 29. PMID: 32993619

Abstract Author(s):

V Lukman, S W Odeyemi, R L Roth, L Mbabala, N Tshililo, N M Vlok, M J B Dewar, C P Kenyon

Article Affiliation:

V Lukman

Abstract:

BACKGROUND: 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.

RESULTS: 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 (IC) of an aqueous root extract of P. sidoides against the kinases indicated SK has an ICof 1.2 μg/ml and GK 1.4 μg/ml. These enzyme targets were further assessed for compound identification from the P. sidoides literature.

CONCLUSION: 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.

Study Type : In Vitro Study

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