Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding

The novel 1,2,3-triazolyl-appended N- and O-heterocycles containing amidine 4–11 and amidoxime 12–22 moiety were prepared and evaluated for their antiproliferative activities in vitro. A...

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Autores principales:	Silvija Maračić, Petra Grbčić, Suresh Shammugam, Marijana Radić Stojković, Krešimir Pavelić, Mirela Sedić, Sandra Kraljević Pavelić, Silvana Raić-Malić
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	amidine amidoxime antiproliferative activity DNA binding fluorescence CD spectroscopy Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/8cb32eaeb4324ad7a8d052bd4effcb96
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spelling	oai:doaj.org-article:8cb32eaeb4324ad7a8d052bd4effcb962021-11-25T18:29:31ZAmidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding10.3390/molecules262270601420-3049https://doaj.org/article/8cb32eaeb4324ad7a8d052bd4effcb962021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7060https://doaj.org/toc/1420-3049The novel 1,2,3-triazolyl-appended <i>N</i>- and <i>O</i>-heterocycles containing amidine <b>4</b>–<b>11</b> and amidoxime <b>12</b>–<b>22</b> moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine <b>5</b> and coumarine amidine <b>11</b> had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC<sub>50</sub> values in the nM range. Although compound <b>5</b> was toxic to non-tumor HFF cells, compound <b>11</b> showed certain selectivity. From the amidoxime series, quinoline amidoximes <b>18</b> and <b>20</b> showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound <b>20</b> that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds <b>5</b> and <b>10</b> most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds <b>6</b>, <b>9</b> and <b>11</b> bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.Silvija MaračićPetra GrbčićSuresh ShammugamMarijana Radić StojkovićKrešimir PavelićMirela SedićSandra Kraljević PavelićSilvana Raić-MalićMDPI AGarticleamidineamidoximeantiproliferative activityDNA bindingfluorescenceCD spectroscopyOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7060, p 7060 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amidine amidoxime antiproliferative activity DNA binding fluorescence CD spectroscopy Organic chemistry QD241-441
spellingShingle	amidine amidoxime antiproliferative activity DNA binding fluorescence CD spectroscopy Organic chemistry QD241-441 Silvija Maračić Petra Grbčić Suresh Shammugam Marijana Radić Stojković Krešimir Pavelić Mirela Sedić Sandra Kraljević Pavelić Silvana Raić-Malić Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
description	The novel 1,2,3-triazolyl-appended <i>N</i>- and <i>O</i>-heterocycles containing amidine <b>4</b>–<b>11</b> and amidoxime <b>12</b>–<b>22</b> moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine <b>5</b> and coumarine amidine <b>11</b> had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC<sub>50</sub> values in the nM range. Although compound <b>5</b> was toxic to non-tumor HFF cells, compound <b>11</b> showed certain selectivity. From the amidoxime series, quinoline amidoximes <b>18</b> and <b>20</b> showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound <b>20</b> that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds <b>5</b> and <b>10</b> most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds <b>6</b>, <b>9</b> and <b>11</b> bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.
format	article
author	Silvija Maračić Petra Grbčić Suresh Shammugam Marijana Radić Stojković Krešimir Pavelić Mirela Sedić Sandra Kraljević Pavelić Silvana Raić-Malić
author_facet	Silvija Maračić Petra Grbčić Suresh Shammugam Marijana Radić Stojković Krešimir Pavelić Mirela Sedić Sandra Kraljević Pavelić Silvana Raić-Malić
author_sort	Silvija Maračić
title	Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
title_short	Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
title_full	Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
title_fullStr	Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
title_full_unstemmed	Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding
title_sort	amidine- and amidoxime-substituted heterocycles: synthesis, antiproliferative evaluations and dna binding
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8cb32eaeb4324ad7a8d052bd4effcb96
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Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding

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