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Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles

A series of 6-amidinobenzothiazoles, linked via phenoxymethylene or directly to the 1,2,3-triazole ring with a p-substituted phenyl or benzyl moiety, were synthesised and evaluated in vitro against four human tumour cell lines and the protozoan parasite Trypanosoma brucei. The influence of the type...

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Autores principales: Racané, Livio, Rep, Valentina, Kraljević Pavelić, Sandra, Grbčić, Petra, Zonjić, Iva, Radić Stojković, Marijana, Taylor, Martin C., Kelly, John M., Raić-Malić, Silvana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409973/
https://www.ncbi.nlm.nih.gov/pubmed/34455887
http://dx.doi.org/10.1080/14756366.2021.1959572
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author Racané, Livio
Rep, Valentina
Kraljević Pavelić, Sandra
Grbčić, Petra
Zonjić, Iva
Radić Stojković, Marijana
Taylor, Martin C.
Kelly, John M.
Raić-Malić, Silvana
author_facet Racané, Livio
Rep, Valentina
Kraljević Pavelić, Sandra
Grbčić, Petra
Zonjić, Iva
Radić Stojković, Marijana
Taylor, Martin C.
Kelly, John M.
Raić-Malić, Silvana
author_sort Racané, Livio
collection PubMed
description A series of 6-amidinobenzothiazoles, linked via phenoxymethylene or directly to the 1,2,3-triazole ring with a p-substituted phenyl or benzyl moiety, were synthesised and evaluated in vitro against four human tumour cell lines and the protozoan parasite Trypanosoma brucei. The influence of the type of amidino substituent and phenoxymethylene linker on antiproliferative and antitrypanosomal activities was observed, showing that the imidazoline moiety had a major impact on both activities. Benzothiazole imidazoline 14a, which was directly connected to N-1-phenyl-1,2,3-triazole, had the most potent growth-inhibitory effect (IC(50) = 0.25 µM) on colorectal adenocarcinoma (SW620), while benzothiazole imidazoline 11b, containing a phenoxymethylene linker, exhibited the best antitrypanosomal potency (IC(90) = 0.12 µM). DNA binding assays showed a non-covalent interaction of 6-amidinobenzothiazole ligands, indicating both minor groove binding and intercalation modes of DNA interaction. Our findings encourage further development of novel structurally related 6-amidino-2-arylbenzothiazoles to obtain more selective anticancer and anti-HAT agents.
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spelling pubmed-84099732021-09-02 Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles Racané, Livio Rep, Valentina Kraljević Pavelić, Sandra Grbčić, Petra Zonjić, Iva Radić Stojković, Marijana Taylor, Martin C. Kelly, John M. Raić-Malić, Silvana J Enzyme Inhib Med Chem Research Paper A series of 6-amidinobenzothiazoles, linked via phenoxymethylene or directly to the 1,2,3-triazole ring with a p-substituted phenyl or benzyl moiety, were synthesised and evaluated in vitro against four human tumour cell lines and the protozoan parasite Trypanosoma brucei. The influence of the type of amidino substituent and phenoxymethylene linker on antiproliferative and antitrypanosomal activities was observed, showing that the imidazoline moiety had a major impact on both activities. Benzothiazole imidazoline 14a, which was directly connected to N-1-phenyl-1,2,3-triazole, had the most potent growth-inhibitory effect (IC(50) = 0.25 µM) on colorectal adenocarcinoma (SW620), while benzothiazole imidazoline 11b, containing a phenoxymethylene linker, exhibited the best antitrypanosomal potency (IC(90) = 0.12 µM). DNA binding assays showed a non-covalent interaction of 6-amidinobenzothiazole ligands, indicating both minor groove binding and intercalation modes of DNA interaction. Our findings encourage further development of novel structurally related 6-amidino-2-arylbenzothiazoles to obtain more selective anticancer and anti-HAT agents. Taylor & Francis 2021-08-30 /pmc/articles/PMC8409973/ /pubmed/34455887 http://dx.doi.org/10.1080/14756366.2021.1959572 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Racané, Livio
Rep, Valentina
Kraljević Pavelić, Sandra
Grbčić, Petra
Zonjić, Iva
Radić Stojković, Marijana
Taylor, Martin C.
Kelly, John M.
Raić-Malić, Silvana
Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title_full Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title_fullStr Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title_full_unstemmed Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title_short Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
title_sort synthesis, antiproliferative and antitrypanosomal activities, and dna binding of novel 6-amidino-2-arylbenzothiazoles
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409973/
https://www.ncbi.nlm.nih.gov/pubmed/34455887
http://dx.doi.org/10.1080/14756366.2021.1959572
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