Paper Search
Main Menu
Homepage
Submission
Papers In Press
Search
Information for Contributors
Introducing the Journal
Board of Journal of Science
Contact address
 
Select by Volumes


 
 
 
 
 
 
 
SCImago Journal & Country Rank
 
0.39
2018CiteScore
 
25th percentile
Powered by  Scopus
Home > Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors
 
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors
Paper Type
Contributed Paper
Title
Porphyrin-acridine Hybrid Compounds as Potential Candidates for Topoisomerase II Alpha Inhibitors
Author
Hubbi Nashrullah Muhammad, Sophi Damayanti and Daryono Hadi Tjahjono
Email
hubbi@fa.itb.ac.id
Abstract:
 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.

 
Start & End Page
455 - 472
Received Date
2019-08-13
Accepted Date
2019-12-03
Full Text
Download
Correspondence:
Author Name
Hubbi Nashrullah Muhammad - School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia.
Keyword:
Keyword
porphyrin, acridine, topoisomerase II alpha, molecular dynamics,
Volume
Vol.47 No.3 (May 2020)
 




Besucherzähler-Counter.com