Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator

Naphthalene substituents enhance mutagenicity of N-acyloxy-N-alkoxyamides towards S. typhimurium TA100 to the extent of 4 log P, most likely through intercalative binding to DNA.

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Correction: Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator

Organic & Biomolecular Chemistry ◽

10.1039/c6ob90099b ◽

2016 ◽

Vol 14 (28) ◽

pp. 6871-6871

Author(s):

Tony M. Banks ◽

Samuel F. Clay ◽

Stephen A. Glover ◽

Rhiannon R. Schumacher

Keyword(s):

Dna Intercalation ◽

Dna Intercalator

Correction for ‘Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator’ by Tony M. Banks, et al., Org. Biomol. Chem., 2016, 14, 3699–3714.

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5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190621120304 ◽

2019 ◽

Vol 19 (13) ◽

pp. 1075-1091 ◽

Cited By ~ 4

Author(s):

Karla Mirella Roque Marques ◽

Maria Rodrigues do Desterro ◽

Sandrine Maria de Arruda ◽

Luiz Nascimento de Araújo Neto ◽

Maria do Carmo Alves de Lima ◽

...

Keyword(s):

Cell Cycle ◽

Antitumor Activity ◽

Cell Line ◽

Mitochondrial Membrane ◽

In Vitro Cytotoxicity ◽

Dna Intercalation ◽

Phase Cell ◽

Fluorescence Studies ◽

In Silico Studies

Background: Considering the need for the development of new antitumor drugs, associated with the great antitumor potential of thiophene and thiosemicarbazonic derivatives, in this work we promote molecular hybridization approach to synthesize new compounds with increased anticancer activity. Objective: Investigate the antitumor activity and their likely mechanisms of action of a series of N-substituted 2-(5-nitro-thiophene)-thiosemicarbazone derivatives. Methods: Methods were performed in vitro (cytotoxicity, cell cycle progression, morphological analysis, mitochondrial membrane potential evaluation and topoisomerase assay), spectroscopic (DNA interaction studies), and in silico studies (docking and molecular modelling). Results: Most of the compounds presented significant inhibitory activity; the NCIH-292 cell line was the most resistant, and the HL-60 cell line was the most sensitive. The most promising compound was LNN-05 with IC50 values ranging from 0.5 to 1.9 µg.mL-1. The in vitro studies revealed that LNN-05 was able to depolarize (dose-dependently) the mitochondrial membrane, induceG1 phase cell cycle arrest noticeably, promote morphological cell changes associated with apoptosis in chronic human myelocytic leukaemia (K-562) cells, and presented no topoisomerase II inhibition. Spectroscopic UV-vis and molecular fluorescence studies showed that LNN compounds interact with ctDNA forming supramolecular complexes. Intercalation between nitrogenous bases was revealed through KI quenching and competitive ethidium bromide assays. Docking and Molecular Dynamics suggested that 5-nitro-thiophene-thiosemicarbazone compounds interact against the larger DNA groove, and corroborating the spectroscopic results, may assume an intercalating interaction mode. Conclusion: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies.

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FRET-Based Probe for High-Throughput DNA Intercalator Drug Discovery and In Vivo Imaging

ACS Sensors ◽

10.1021/acssensors.1c00167 ◽

2021 ◽

Author(s):

Chandrashekhar U. Murade ◽

Samata Chaudhuri ◽

Ibtissem Nabti ◽

Hala Fahs ◽

Fatima S. M. Refai ◽

...

Keyword(s):

Drug Discovery ◽

High Throughput ◽

In Vivo Imaging ◽

Dna Intercalator

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A trap potential model investigation of the optical activity induced in dye-DNA intercalation complexes

Chemical Physics ◽

10.1016/0301-0104(88)87211-2 ◽

1988 ◽

Vol 120 (1) ◽

pp. 79-89 ◽

Cited By ~ 2

Author(s):

Mamoru Kamiya

Keyword(s):

Optical Activity ◽

Potential Model ◽

Dna Intercalation ◽

Model Investigation ◽

Intercalation Complexes ◽

Trap Potential

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Fast photoinduced electron transfer through DNA intercalation.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.91.12.5315 ◽

1994 ◽

Vol 91 (12) ◽

pp. 5315-5319 ◽

Cited By ~ 91

Author(s):

C. J. Murphy ◽

M. R. Arkin ◽

N. D. Ghatlia ◽

S. Bossmann ◽

N. J. Turro ◽

...

Keyword(s):

Electron Transfer ◽

Photoinduced Electron Transfer ◽

Dna Intercalation

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S16020 pyridocarbazole derivatives display high activity to lung cancer cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211214104926 ◽

2021 ◽

Vol 21 ◽

Author(s):

Gabriela Chabowska ◽

Helena Moreira ◽

Beata Tylińska ◽

Ewa Barg

Keyword(s):

Cell Viability ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Wide Spectrum ◽

A549 Cells ◽

Biological Evaluation ◽

Dna Intercalation ◽

P Glycoprotein ◽

Low Toxicity ◽

And Migration

Background: Despite the dynamic development of medicine, globally cancer diseases remain the second leading cause of death. Therefore, there is a strong necessity to improve chemotherapy regimens and search for new anticancer agents. Pyridocarbazoles are compounds with confirmed antitumor properties based on multimodal mechanisms, i.a. DNA intercalation and topoisomerase II-DNA complex inhibition. One of them, S16020, displayed a wide spectrum of activity. Objective: The aim of the study was to investigate the antitumor potency of six S16020 derivatives, synthesized according to the SAR (structure-activity relationship) method. Methods: The biological evaluation included influence on cancer cell viability, proliferation, and migration, as well as P-glycoprotein activity. NHDF, A549, MCF-7, LoVo, and LoVo/DX cell lines were used in the study. Results: All derivatives displayed low toxicity to normal (NHDF) cells at 1 and 2 µM (≤ 20% of cell growth inhibition). The highest reduction in cell viability was noted in A549 cells which was accompanied by significant disruption of cells proliferation and motility. Compound 1 exhibited the strongest cytotoxic, antiproliferative, and antimigratory effects, higher than the reference olivacine. A significant reduction in P-glycoprotein activity was found for derivatives 6 and 1. Conclusion: S16020 derivatives could be considered as potential candidates for new anticancer drugs.

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