<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>In order to increase the effectiveness of cancer treatment, new compounds with potential anticancer activities are synthesized and screened. Here we present the screening of a new class of compounds, 1-(2-picolyl)-, 4-(2-picolyl)-, 1-(2-pyridyl)-, and 4-(2-pyridyl)-3-methyl-1,2,3-triazolium salts and ‘parent’ 1,2,3-triazole precursors.</p></sec><sec><h3>Methods</h3><p>Cytotoxic activity of new compounds was determined by spectrophotometric MTT assay on several tumour and one normal cell line. Effect of the selected compound to bind double stranded DNA (ds DNA) was examined by testing its influence on thermal stability of calf thymus DNA while its influence on cell cycle was determined by flow cytometric analysis. Generation of reactive oxygen species (ROS) was determined by addition of specific substrate 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H<sub>2</sub>DCFDA).</p></sec><sec><h3>Results</h3><p>Parent triazoles were largely inactive, while some of the triazolium salts were highly cytotoxic for HeLa cells. Triazolium salts exhibited high cell-type dependent cytotoxicity against different tumour cells. Selected compound (4-(4-methoxyphenyl)-3-methyl-1-(2-picolyl)-1<italic>H</italic>-1,2,3-triazolium hexafluorophosphate(V) (2b) was significantly more cytotoxic against tumour cells than to normal cells, with very high therapeutic index 7.69 for large cell lung carcinoma H460 cells. Additionally, this compound was similarly cytotoxic against parent laryngeal carcinoma HEp-2 cells and their drug resistant 7T subline, suggesting the potential of this compound in treatment of drug resistant cancers. Compound 2b arrested cells in the G1 phase of the cell cycle. It did not bind ds DNA, but induced ROS in treated cells, which further triggered cell death.</p></sec><sec><h3>Conclusions</h3><p>Our results suggest that the ‘click’ triazolium salts are worthy of further investigation as anti-cancer agents.</p></sec></abstract>

BackgroundIn order to increase the effectiveness of cancer treatment, new compounds with potential anticancer activities are synthesized and screened. Here we present the screening of a new class of compounds, 1-(2-picolyl)-, 4-(2-picolyl)-, 1-(2-pyridyl)-, and 4-(2-pyridyl)-3-methyl-1,2,3-triazolium salts and ‘parent’ 1,2,3-triazole precursors.MethodsCytotoxic activity of new compounds was determined by spectrophotometric MTT assay on several tumour and one normal cell line. Effect of the selected compound to bind double stranded DNA (ds DNA) was examined by testing its influence on thermal stability of calf thymus DNA while its influence on cell cycle was determined by flow cytometric analysis. Generation of reactive oxygen species (ROS) was determined by addition of specific substrate 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA).ResultsParent triazoles were largely inactive, while some of the triazolium salts were highly cytotoxic for HeLa cells. Triazolium salts exhibited high cell-type dependent cytotoxicity against different tumour cells. Selected compound (4-(4-methoxyphenyl)-3-methyl-1-(2-picolyl)-1H-1,2,3-triazolium hexafluorophosphate(V) (2b) was significantly more cytotoxic against tumour cells than to normal cells, with very high therapeutic index 7.69 for large cell lung carcinoma H460 cells. Additionally, this compound was similarly cytotoxic against parent laryngeal carcinoma HEp-2 cells and their drug resistant 7T subline, suggesting the potential of this compound in treatment of drug resistant cancers. Compound 2b arrested cells in the G1 phase of the cell cycle. It did not bind ds DNA, but induced ROS in treated cells, which further triggered cell death.ConclusionsOur results suggest that the ‘click’ triazolium salts are worthy of further investigation as anti-cancer agents.

Discovery of ‘click’ 1,2,3-triazolium salts as potential anticancer drugs

Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia

Department for Translational Medicine, Children’s Hospital Srebrnjak, Zagreb, Croatia

Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia

Department for Oncoplastic and Reconstructive Surgery, University Hospital for Tumors, University Clinical Hospital Centre Sisters of Mercy, Zagreb, Croatia

Radiology and Oncology

BackgroundIn order to increase the effectiveness of cancer treatment, new compounds with potential anticancer activities are synthesized and screened. Here we...

Discovery of ‘click’ 1,2,3-triazolium salts as potential anticancer drugs

Article Category: Research Article

Published Online: Jul 19, 2016

Page range: 280 - 288

Received: Nov 23, 2015

Accepted: Mar 17, 2016

DOI: https://doi.org/10.1515/raon-2016-0027

© Radiol Oncol 2016

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