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Assessment of Molecular Binding of Podophyllotoxin Analogues into ATPase Domain of Topoisomerase Ⅱ Using Docking-MM-GB/SA Approach
並列摘要
Synthetic analogues of Podophyllotoxin have been used to create efficient safer anticancer drugs. One hundred twenty six analogues using combinatorial design with structural modifications of the scaffold structure of podophyllotoxin are herein described. Molecular interaction and binding affinities with ATPase domain of human DNA Topoisomerase Ⅱ (TP-Ⅱ) using docking-MM-GB/SA screening are illustrated. Results showed that these analogues docked in a similar position and orientation on the ATPase domain of TP-II. A linear correlation (r^2=0.5707) was observed between the calculated free energy of binding (FEB) and experimental IC50 for the inhibitors, suggesting that theses inhibitors bind weakly with TP-II. Three H-bonds between podophyllotoxin analogues (trans lactones) and DNA topoisomerase Ⅱ were observed. The vdW energy estimated by generalized born/surface area (GB/SA) plays an important role in the binding affinity of podophyllotoxin analogues. Out of 126 derivatives, lactones tetralines were found to be the most potent in general in comparison with the non-lactones tetralines and non-lactones cyclolignans. This work addresses to modify the lactone moiety and prepare synthetic analogues with heteroatoms at different positions of the podophyllotoxin and further screening for a successful candidate drug in a computer-aided rational drug design.
延伸閱讀
- Chen, C. Y., Liao, H. L., & Chung, J. C. (1999). Amplification of virD1 and opine synthase genes from tumorigenic rose and aster strains of Agrobacterium in Taiwan by polymerase chain reaction. 植物病理學會刊, 8(4), 143-148. https://doi.org/10.6649/PPB.199912_8(4).0003
- D'Annessa, I., Tesauro, C., Fiorani, P., Chillemi, G., Castelli, S., Vassallo, O., Capranico, G., & Desideri, A. (2012). Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly-Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin. Journal of Amino Acids, 2012(), 3-10. https://doi.org/10.1155/2012/206083
- Ningrum, S. (2020). An Exploration of Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Gastrointestinal Protease Hydrolysate of Milk using Modified Bioassay-Guided Fractionation Approach [master's thesis, National Pingtung University of Science and Technology]. Airiti Library. https://doi.org/10.6346/NPUST202000346
- Chern, Y. J., Chiou, J. Y., Lai, H. L., & Tsai, M. H. (1995). Regulation of Adenylyl Cyclase Type Ⅵ Activity during Desensitization of the A2a Adenosine Receptor-Mediated Cyclic AMP Response: Role for Protein Phosphatase 2A. 藥物食品檢驗局調查研究年報, (), 47-54. https://doi.org/10.6946/ASRNL.199509.0047
- 劉英志（2005）。Protein Tyrosine Phosphatase PTP-PEST is cleaved and activated through Caspase-3-mediated pathwayImplication of a Novel Regulatory Mechanism during Apoptosis〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2005.10383