A Natural Anticancer Agent Thaspine Targets Human Topoisomerase IB

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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A Natural Anticancer Agent Thaspine Targets Human Topoisomerase IB

Anti-Cancer Agents in Medicinal Chemistry, 13(2): 356-363.

Author(s): Silvia Castelli, Prafulla Katkar, Oscar Vassallo, Mattia Falconi, Stig Linder and Alessandro Desideri.

Affiliation: Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, Italy.


The different steps of the topoisomerase I catalytic cycle have been analyzed in the presence of the plant alkaloid thaspine (1- (2-(Dimethylamino)ethyl)-3,8-dimethoxychromeno[5,4,3-cde]chromene-5,10-dione), known to induce apoptosis in colon carcinoma cells. The experiments indicate that thaspine inhibits both the cleavage and the religation steps of the enzyme reaction. The inhibition is reversible and the effect is enhanced upon pre-incubation. Molecular docking simulations of thaspine over topoisomerase I, in the presence or absence of the DNA substrate, show that thaspine, when interacting with the enzyme alone in the closed or in the open state, can bind in proximity of the active residues preventing the cleavage reaction, whilst when docked with the enzyme-DNA cleavable complex intercalates between the DNA bases in a way similar to that found for camptothecin, explaining its religation inhibition. These results unequivocally demonstrate that thaspine targets human topoisomerase I .


Camptothecin, Human topoisomerase IB, Inhibitor, Molecular docking, Thaspine.

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Article Details

Volume: 13
Issue Number: 2
First Page: 356
Last Page: 363
Page Count: 8
DOI: 10.2174/1871520611313020021
Price: $58

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