Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6

• Main Author: Yew, Wei Ni
• Other Authors: Julien Lescar
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/171865
• Institution: Nanyang Technological University

Malaria is a potentially life-threatening disease caused by Plasmodium parasites. While existing drugs have been effective, the emergence of drug resistance necessitates the identification of new drug targets and the development of potential drugs. Plasmodium falciparum Protein Kinase 6 (PfPK6) has been genetically identified as a promising new target crucial for the survival of Plasmodium falciparum. This study aimed to validate the binding of Compound 1 to purified PfPK6, assess the potential inhibitory effects of Compound 1 on PfPK6, and explore its mechanism of action within the PfPK6 binding site. Through differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), it was confirmed that Compound 1 binds to PfPK6 with moderate affinity. Additionally, enzymatic assay provided evidence of Compound 1 inhibiting PfPK6 activity. Despite numerous attempts, the atomic interaction between Compound 1 and PfPK6 has yet to unravel due to challenges in co-crystallizing PfPK6 with Compound 1 and crystallizing PfPK6 itself. Nonetheless, this study has demonstrated the ability of Compound 1 to bind to and inhibit PfPK6, shedding light on its potential as a therapeutic target for combating malaria.