Inhibition of human DNA topoisomerase IB by a Cyclometalated Gold III compound: Analysis on the different steps of the enzyme catalytic cycle

2011 ◽  
Vol 516 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Silvia Castelli ◽  
Oscar Vassallo ◽  
Prafulla Katkar ◽  
Chi-Ming Che ◽  
Raymond Wai-Yin Sun ◽  
...  
Keyword(s):  
Catalytic Cycle ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib

scholarly journals In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB

2021 ◽  
Vol 22 (14) ◽  
pp. 7455
Author(s):  
Bini Chhetri Soren ◽  
Jagadish Babu Dasari ◽  
Alessio Ottaviani ◽  
Beatrice Messina ◽  
Giada Andreotti ◽  
...  
Keyword(s):  
Enzyme Reaction ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib ◽  
Topological State ◽  
Cleavage Step ◽  
Dynamics Simulations ◽  
In Silico Characterization ◽  
Dna Complex

Human DNA topoisomerase IB controls the topological state of supercoiled DNA through a complex catalytic cycle that consists of cleavage and religation reactions, allowing the progression of fundamental DNA metabolism. The catalytic steps of human DNA topoisomerase IB were analyzed in the presence of a drug, obtained by the open-access drug bank Medicines for Malaria Venture. The experiments indicate that the compound strongly and irreversibly inhibits the cleavage step of the enzyme reaction and reduces the cell viability of three different cancer cell lines. Molecular docking and molecular dynamics simulations suggest that the drug binds to the human DNA topoisomerase IB-DNA complex sitting inside the catalytic site of the enzyme, providing a molecular explanation for the cleavage-inhibition effect. For all these reasons, the aforementioned drug could be a possible lead compound for the development of an efficient anti-tumor molecule targeting human DNA topoisomerase IB.

Comparative studies of oxindolimine-metal complexes as inhibitors of human DNA topoisomerase IB

2018 ◽  
Vol 186 ◽  
pp. 85-94 ◽  
Author(s):  
Silvia Castelli ◽  
Marcos Brown Gonçalves ◽  
Prafulla Katkar ◽  
Gabriela Cristina Stuchi ◽  
Ricardo Alexandre Alves Couto ◽  
...  
Keyword(s):  
Metal Complexes ◽  
Comparative Studies ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib

Molecular modelling studies on the interactions of human DNA topoisomerase IB with pyridoxal-compounds

Biochimie ◽  
2007 ◽  
Vol 89 (4) ◽  
pp. 468-473 ◽  
Author(s):  
Serge Christmann-Franck ◽  
Serge Fermandjian ◽  
Gilles Mirambeau ◽  
P. Arsène Der Garabedian
Keyword(s):  
Molecular Modelling ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib ◽  
Molecular Modelling Studies ◽  
Modelling Studies

scholarly journals A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance

2008 ◽  
Vol 36 (17) ◽  
pp. 5635-5644 ◽  
Author(s):  
Carmen Losasso ◽  
Erica Cretaio ◽  
Paola Fiorani ◽  
Ilda D’Annessa ◽  
Giovanni Chillemi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
Single Mutation ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib

Gold(III), Cyclometalated Compound, Inhibition of Human DNA Topoisomerase IB

2013 ◽  
pp. 927-932
Author(s):  
Silvia Castelli ◽  
Oscar Vassallo ◽  
Prafulla Katkar ◽  
Chi-Ming Che ◽  
Raymond Wai-Yin Sun ◽  
...  
Keyword(s):  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib

Inhibition of human DNA topoisomerase IB by nonmutagenic ruthenium(ii)-based compounds with antitumoral activity

Metallomics ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 179-192 ◽  
Author(s):  
Mariana S. de Camargo ◽  
Monize M. da Silva ◽  
Rodrigo S. Correa ◽  
Sara D. Vieira ◽  
Silvia Castelli ◽  
...  
Keyword(s):  
Antitumoral Activity ◽  
Dna Topoisomerase ◽  
Human Dna ◽  
Topoisomerase Ib

New cytotoxic ruthenium(ii) compounds with mercaptopyridine derivatives inhibit human DNA topoisomerase IB and interact moderately with DNA and BSA macromolecules.

scholarly journals First total synthesis of the (±)-2-methoxy-6-heptadecynoic acid and related 2-methoxylated analogs as effective inhibitors of the Leishmania topoisomerase IB enzyme

2012 ◽  
Vol 84 (9) ◽  
pp. 1867-1875 ◽  
Author(s):  
Néstor M. Carballeira ◽  
Michelle Cartagena ◽  
Fengyu Li ◽  
Zhongfang Chen ◽  
Christopher F. Prada ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Total Synthesis ◽  
Leishmania Donovani ◽  
Dna Topoisomerase ◽  
Triple Bonds ◽  
Weak Intermolecular Interactions ◽  
Topoisomerase Ib ◽  
Effective Inhibition ◽  
Acetylenic Fatty Acid

The fatty acids (±)-2-methoxy-6Z-heptadecenoic acid, (±)-2-methoxy-6-hepta-decynoic acid, and (±)-2-methoxyheptadecanoic acid were synthesized and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme (LdTopIB) determined. Both 2-OMe-17:1 fatty acids were synthesized from 4-bromo-1-pentanol, the olefinic fatty acid in 10 steps and in 7 % overall yield, while the acetylenic fatty acid in 7 steps and in 14 % overall yield. The 2-OMe-17:0 acid was prepared in 6 steps and in 42 % yield from 1-hexa-decanol. The 2-OMe-17:1 acids inhibited LdTopIB, with the acetylenic acid displaying an EC50 = 16.6 ± 1.1 μM, but the 2-OMe-17:0 acid did not inhibit LdTopIB. The (±)-2-methoxy-6Z-heptadecenoic acid preferentially inhibited LdTopIB over the human TopIB enzyme. Unsaturation seems to be a prerequisite for effective inhibition, rationalized in terms of weak intermolecular interactions between the active site of LdTopIB and either the double or triple bonds of the fatty acids. Toxicity toward Leishmania donovani promastigotes was also investigated, resulting in the order acetylenic > olefinic > saturated with the (±)-2-methoxy-6-heptadecynoic acid displaying an EC50 = 74.0 ± 17.1 μM. Our results indicate that α-methoxylation decreases the toxicity of C17:1 fatty acids toward L. donovani promastigotes, but improves their selectivity index.

103 Site-directed mutagenesis of human DNA topoisomerase IIβ

1997 ◽  
Vol 25 (4) ◽  
pp. S638-S638 ◽  
Author(s):  
KATHERINE L. MARSH ◽  
EMMA L. MECZES ◽  
RONALD THORN ◽  
RICHARD MARSHALL ◽  
CAROLINE A. AUSTIN
Keyword(s):  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Dna Topoisomerase ◽  
Human Dna

scholarly journals Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect

2013 ◽  
Vol 85 (10) ◽  
pp. 1433-1440 ◽  
Author(s):  
Christopher F. Prada ◽  
Raquel Álvarez-Velilla ◽  
Rafael Balaña-Fouce ◽  
Carlos Prieto ◽  
Estefania Calvo-Álvarez ◽  
...  
Keyword(s):  
Dna Topoisomerase ◽  
Topoisomerase Ib
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