Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives

doi:10.3390/molecules181215035

Paper

Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives

Published Dec 1, 2013 · Elizabeth Almeida Lafayette, S. M. V. de Almeida, M. G. da Rocha Pitta

Molecules

Q1 SJR score

45

Citations

0

Influential Citations

Open Access PDF Full text Semantic Scholar

Abstract

Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 104 to 6.01 × 104 M−1. UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.

In Vitro Study

Study Snapshot

Thiazacridine and imidazacridine derivatives show promising tumor suppressor activity in cancer cells, binding to DNA and inhibiting human topoisomerase I.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives

Sign up to use Study Snapshot

References

Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives.

Thiazacridine derivatives inhibit DNA topoisomerase I activity and induce tumor cell death through apoptotic pathways in human colon carcinoma HCT-8 cells.

Drugging topoisomerases: lessons and challenges.

Topoisomerase inhibitors are effective anticancer drugs, but face challenges in discovering and precise use, including targeted tumor delivery and pharmacodynamic biomarker monitoring.

Determining the mode of interaction of calf thymus DNA with the drug sumatriptan using voltammetric and spectroscopic techniques.

Sumatriptan intercalates between DNA base pairs, increasing specific viscosity and causing changes in the CD and UV-vis spectra of calf thymus DNA.

Binding studies of the antidiabetic drug, metformin to calf thymus DNA using multispectroscopic methods.

Metformin's interaction with calf thymus DNA is exothermic and surface-bound, with a binding constant of 8.3 10 4 M 1 and stabilization of the right-handed B form of CT-DNA.

3,6-bis(3-alkylguanidino)acridines as DNA-intercalating antitumor agents.

3,6-bis(3-alkylguanidino) acridines show potential as effective DNA-intercalating antitumor agents, with the hexyl derivative 6e being the most cytotoxic.

Citations

Exploring the therapeutic potential of acridines: Synthesis, structure, and biological applications.

Acridines and their derivatives show potential in treating various diseases, with antitumor activity being the most studied aspect.

Spectroscopic exploration of mode of binding of ctDNA and BSA with acridone alkaloids isolated from Zanthoxylum leprieurii (Rutaceae).

Acridonic alkaloids from Zanthoxylum leprieurii fruits show affinity with both DNA and BSA, providing clues to their mechanisms of action and potential anticancer activities.

Novel Antipyrine Substituted 4-Thiazolidinones: Synthesis, DNA Binding and Topoisomerase Inhibition Activities, and in-silico Studies

Novel antipyrine-substituted 4-thiazolidinones show DNA binding and topoisomerase I inhibitory effects, with potential for drug-like properties and in-silico studies.

Voltammetric studies on the interaction of ds-DNA with anti-cancer agents imatinib and erlotinib - Comparison of Au and Pt nanoparticle effects to drug-DNA complex formation

Au + Pt nanoparticles significantly affect the binding constant value of anti-cancer drugs imatinib and erlotinib to ds-DNA, with binding modes potentially being intercalation and groove binding.

New benzothienopyran and benzothienopyranopyrimidine derivatives as topoisomerase I inhibitors: Design, synthesis, anticancer screening, apoptosis induction and molecular modeling studies.

New benzothienopyran and benzothienopyranopyrimidine derivatives show promising potential as topoisomerase I inhibitors, with compounds 4d, 5b, and 6f showing broad spectrum and potent anticancer efficacy.

Design, synthesis, structural investigation and binding study of 2-pyridone-based pharmaceutical precursor with DNA

Four pyridone-based fleximers show promising binding affinities with different receptors and DNA, suggesting potential for in vivo/vitro drug development.

Acridine as an Anti-Tumour Agent: A Critical Review

Acridine derivatives show potential as anti-cancer drugs, but their clinical application is limited due to side effects.