Accelerated approach of discovering plant-derived drug leads for treatment of tuberculosis

Abstract

The bioprospecting research group at CSIR biosciences undertakes research that taps into South Africa’s plant biodiversity with the aim of discovering natural products that can be used to develop new medicines effective against tuberculosis (TB). To achieve this, the group has implemented the accelerated 96 well plate fractionation approach (Figure 1) to speed up the identification of active ingredients and interesting chemical scaffolds for subsequent medicinal chemistry developments, and to prevent the repeated discovery of known and undesired compounds, thereby saving time and resources. To demonstrate the effectiveness of the accelerated approach, one of the organic plant extracts that displayed good anti-TB activity (MIC ≤ 250 μg/ml) was fractionated and screened for biological activity. The active fractions were analysed by UPLC-TO F-DADMS for UV, accurate mass and MS-MS fragmentation data to identify the compounds present. By using the data to search the Dictionary of natural products, scientists could identify the compound responsible for activity and could make upfront go/ no go decisions, depending on the compound’s desirability as a drug lead