Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies

The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-a...

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Autores: Jablonski, A., Matczak, K., Koceva-Chyla, A., Durka, K., Steverding, D., Jakubiec-Krzesniak, K., Solecka, J., Trzybinski, D., Wozniak, K., Andreu, V., Mendoza, G., Arruebo, M., Kochel, K., Krawczyk, B., Szczukocki, D., Kowalski, K.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:65304
Acceso en línea:http://zaguan.unizar.es/record/65304
Access Level:acceso abierto
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spelling Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studiesJablonski, A.Matczak, K.Koceva-Chyla, A.Durka, K.Steverding, D.Jakubiec-Krzesniak, K.Solecka, J.Trzybinski, D.Wozniak, K.Andreu, V.Mendoza, G.Arruebo, M.Kochel, K.Krawczyk, B.Szczukocki, D.Kowalski, K.The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3-4 µM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8-64 µg/mL and seemed to be the result of induced cell shrinking.2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://zaguan.unizar.es/record/65304reponame:Zaguán. Repositorio Digital de la Universidad de Zaragozainstname:Universidad de ZaragozaInglésinfo:eu-repo/semantics/openAccessoai:zaguan.unizar.es:653042026-05-29T13:59:51Z
dc.title.none.fl_str_mv Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
title Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
spellingShingle Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
Jablonski, A.
title_short Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
title_full Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
title_fullStr Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
title_full_unstemmed Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
title_sort Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
dc.creator.none.fl_str_mv Jablonski, A.
Matczak, K.
Koceva-Chyla, A.
Durka, K.
Steverding, D.
Jakubiec-Krzesniak, K.
Solecka, J.
Trzybinski, D.
Wozniak, K.
Andreu, V.
Mendoza, G.
Arruebo, M.
Kochel, K.
Krawczyk, B.
Szczukocki, D.
Kowalski, K.
author Jablonski, A.
author_facet Jablonski, A.
Matczak, K.
Koceva-Chyla, A.
Durka, K.
Steverding, D.
Jakubiec-Krzesniak, K.
Solecka, J.
Trzybinski, D.
Wozniak, K.
Andreu, V.
Mendoza, G.
Arruebo, M.
Kochel, K.
Krawczyk, B.
Szczukocki, D.
Kowalski, K.
author_role author
author2 Matczak, K.
Koceva-Chyla, A.
Durka, K.
Steverding, D.
Jakubiec-Krzesniak, K.
Solecka, J.
Trzybinski, D.
Wozniak, K.
Andreu, V.
Mendoza, G.
Arruebo, M.
Kochel, K.
Krawczyk, B.
Szczukocki, D.
Kowalski, K.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3-4 µM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8-64 µg/mL and seemed to be the result of induced cell shrinking.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://zaguan.unizar.es/record/65304
url http://zaguan.unizar.es/record/65304
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv
publisher.none.fl_str_mv
dc.source.none.fl_str_mv reponame:Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname:Universidad de Zaragoza
instname_str Universidad de Zaragoza
reponame_str Zaguán. Repositorio Digital de la Universidad de Zaragoza
collection Zaguán. Repositorio Digital de la Universidad de Zaragoza
repository.name.fl_str_mv
repository.mail.fl_str_mv
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