ArticleJournal of the American Chemical Society2014
Gold(III) macrocycles: nucleotide-specific unconventional catalytic inhibitors of human topoisomerase I.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 63 citations in OpenAlex.
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- A Cytotoxic Indazole-based Gold(III) Carboxamide Pincer Complex Targeting DNA Through Dual Binding Modes of Groove Binding and Alkylation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Spectroscopic and Computational pH Study of NiMolecules (Basel, Switzerland) · 2023Article
- Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications.Chemical reviews · 2023Review
- A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Is the Way to Fight Cancer Paved with Gold? Metal-Based Carbene Complexes with Multiple and Fascinating Biological Features.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound.PloS one · 2019Article
- Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2018Article
- Transition Metal Intercalators as Anticancer Agents-Recent Advances.International journal of molecular sciences · 2016Review
- A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase.Antimicrobial agents and chemotherapy · 2016Article
- How frequently do clusters occur in hierarchical clustering analysis? A graph theoretical approach to studying ties in proximity.Journal of cheminformatics · 2016Article
- Synthesis, reactivity, and biological activity of gold(I) complexes modified with thiourea-functionalized tyrosine kinase inhibitors.Inorganic chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerase IB (Top1) is a key eukaryotic nuclear enzyme that regulates the topology of DNA during replication and gene transcription. Anticancer drugs that block Top1 are either well-characterized interfacial poisons or lesser-known catalytic inhibitor compounds. Here we describe a new class of cytotoxic redox-stable cationic Au(3+) macrocycles which, through hierarchical cluster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or inhibitors of Top1. Two pivotal enzyme inhibition assays prove that the compounds are true catalytic inhibitors of Top1. Inhibition of human topoisomerase IIα (Top2α) by 3 was 2 orders of magnitude weaker than its inhibition of Top1, confirming that 3 is a type I-specific catalytic inhibitor. Importantly, Au(3+) is essential for both DNA intercalation and enzyme inhibition. Macromolecular simulations show that 3 intercalates directly at the 5'-TA-3' dinucleotide sequence targeted by Top1 via crucial electrostatic interactions, which include π-π stacking and an Au···O contact involving a thymine carbonyl group, resolving the ambiguity of conventional (drug binds protein) vs unconventional (drug binds substrate) catalytic inhibition of the enzyme. Surface plasmon resonance studies confirm the molecular mechanism of action elucidated by the simulations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.