Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors
Chiang Mai Journal of Science
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Faculty of Science, Chiang Mai University
2020
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| Online Access: | https://epg.science.cmu.ac.th/ejournal/dl.php?journal_id=10917 http://cmuir.cmu.ac.th/jspui/handle/6653943832/68743 |
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th-cmuir.6653943832-687432020-06-10T07:12:28Z Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors Hubbi Nashrullah Muhammad Sophi Damayanti Daryono Hadi Tjahjono porphyrin acridine topoisomerase II alpha molecular dynamics Chiang Mai Journal of Science Topoisomerase IIα plays a vital role in regulating DNA replication and transcription, and ensuring the successful unfolding, segregation, and condensation of chromosomes during mitosis. Because of its crucial function, it has become the target of several anticancer drugs that seek to disrupt the cell cycle of cancerous cells. In this study, we explored the potential for porphyrin-acridine hybrid compounds in inhibiting Topoisomerase IIα. We have designed porphyrin-acridine compounds with varying meso-substituents, and modeled their interactions with Topoisomerase IIα through molecular docking and molecular dynamics simulations. The porphyrin-acridine compounds interacted with the DNA at the Topoisomerase-DNA cleavage complex through intercalation and groove binding, assisted by strong hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations show that mono-H2PyP-AC and bis-H2PzP-AC formed stable complexes with their targets. Binding free energy calculations also show that electrostatic interactions formed by the cationic meso substituents contributed to the overall interaction, and that the acridine moiety significantly strengthened the bond between ligand and target. 2020-06-10T07:12:28Z 2020-06-10T07:12:28Z 2020 Chiang Mai Journal of Science 47,3 (May 2020), p.455-472 2465-3845 https://epg.science.cmu.ac.th/ejournal/dl.php?journal_id=10917 http://cmuir.cmu.ac.th/jspui/handle/6653943832/68743 Eng Faculty of Science, Chiang Mai University |
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CMU Intellectual Repository |
| language |
English |
| topic |
porphyrin acridine topoisomerase II alpha molecular dynamics |
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porphyrin acridine topoisomerase II alpha molecular dynamics Hubbi Nashrullah Muhammad Sophi Damayanti Daryono Hadi Tjahjono Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| description |
Chiang Mai Journal of Science |
| author |
Hubbi Nashrullah Muhammad Sophi Damayanti Daryono Hadi Tjahjono |
| author_facet |
Hubbi Nashrullah Muhammad Sophi Damayanti Daryono Hadi Tjahjono |
| author_sort |
Hubbi Nashrullah Muhammad |
| title |
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| title_short |
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| title_full |
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| title_fullStr |
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| title_full_unstemmed |
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors |
| title_sort |
porphyrin-acridine hybrid compounds as potential candidates for topoisomerase ii alpha inhibitors |
| publisher |
Faculty of Science, Chiang Mai University |
| publishDate |
2020 |
| url |
https://epg.science.cmu.ac.th/ejournal/dl.php?journal_id=10917 http://cmuir.cmu.ac.th/jspui/handle/6653943832/68743 |
| _version_ |
1681752687461269504 |