Topoisomerase I (Top1) is an essential enzyme participating to all those processes associated with separation of DNA strands. It manages superhelical tensions through the transient breakage of one strand of duplex DNA, followed by the unwinding of supercoiled DNA. Camptothecins, a class of alkaloids extracted from the wood of a Chinese tree, were found to be potent inhibitors of Topoisomerase I. The National Cancer Institute (NCI) Anti-cancer Agents Mechanism Database contains several camptothecins derivatives, classified as selective Top1 inhibitors. In this work we performed molecular docking studies on 24 camptothecin-like inhibitors present in this database (using Autodock 3.0.5). In order to consider the different orientations of the active site residues, docking was performed using four different structures of a Top1-DNA complex. The results obtained allowed us to analyze some conformations adopted by the inhibitors during active site binding, confirming the role of hydrogen bond and contributed to clarify the loss of activity due to single point mutations.

LAURIA A, IPPOLITO M, ALMERICO AM (2007). Molecular Docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database. JOURNAL OF MOLECULAR MODELING, 13(3), 393-400 [10.1007/s00894-006-0159-2].

Molecular Docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database

LAURIA, Antonino;IPPOLITO, Mario;ALMERICO, Anna Maria
2007-01-01

Abstract

Topoisomerase I (Top1) is an essential enzyme participating to all those processes associated with separation of DNA strands. It manages superhelical tensions through the transient breakage of one strand of duplex DNA, followed by the unwinding of supercoiled DNA. Camptothecins, a class of alkaloids extracted from the wood of a Chinese tree, were found to be potent inhibitors of Topoisomerase I. The National Cancer Institute (NCI) Anti-cancer Agents Mechanism Database contains several camptothecins derivatives, classified as selective Top1 inhibitors. In this work we performed molecular docking studies on 24 camptothecin-like inhibitors present in this database (using Autodock 3.0.5). In order to consider the different orientations of the active site residues, docking was performed using four different structures of a Top1-DNA complex. The results obtained allowed us to analyze some conformations adopted by the inhibitors during active site binding, confirming the role of hydrogen bond and contributed to clarify the loss of activity due to single point mutations.
2007
LAURIA A, IPPOLITO M, ALMERICO AM (2007). Molecular Docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database. JOURNAL OF MOLECULAR MODELING, 13(3), 393-400 [10.1007/s00894-006-0159-2].
File in questo prodotto:
File Dimensione Formato  
Lauria2007_Article_MolecularDockingApproachOnTheT.pdf

Solo gestori archvio

Dimensione 483 kB
Formato Adobe PDF
483 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/26276
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 27
social impact