Cargando…

Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors

New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable...

Descripción completa

Detalles Bibliográficos
Autores principales: El-Zoghbi, Mona S., El-Sebaey, Samiha A., AL-Ghulikah, Hanan A., Sobh, Eman A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930781/
https://www.ncbi.nlm.nih.gov/pubmed/36776024
http://dx.doi.org/10.1080/14756366.2023.2175209
_version_ 1784889105036869632
author El-Zoghbi, Mona S.
El-Sebaey, Samiha A.
AL-Ghulikah, Hanan A.
Sobh, Eman A.
author_facet El-Zoghbi, Mona S.
El-Sebaey, Samiha A.
AL-Ghulikah, Hanan A.
Sobh, Eman A.
author_sort El-Zoghbi, Mona S.
collection PubMed
description New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin. Compounds exhibiting significant cytotoxicity were further selected to study their inhibitory activity on the Topo II enzyme. Compound 4c was the most potent Topo II inhibitor with an IC(50) value of 0.23 ± 0.01 µM, which was 1.4-fold and 3.6-fold higher than the IC(50) values of Etoposide and Doxorubicin. Furthermore, compound 4c showed significant cell cycle disruption and apoptosis on A549 cells compared to control cells. Molecular docking of the most active compounds illustrated proper fitting to the Topo II active site, suggesting that our designed compounds are promising candidates for the development of effective anticancer agents acting through Topo II inhibition.
format Online
Article
Text
id pubmed-9930781
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-99307812023-02-16 Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors El-Zoghbi, Mona S. El-Sebaey, Samiha A. AL-Ghulikah, Hanan A. Sobh, Eman A. J Enzyme Inhib Med Chem Research Paper New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin. Compounds exhibiting significant cytotoxicity were further selected to study their inhibitory activity on the Topo II enzyme. Compound 4c was the most potent Topo II inhibitor with an IC(50) value of 0.23 ± 0.01 µM, which was 1.4-fold and 3.6-fold higher than the IC(50) values of Etoposide and Doxorubicin. Furthermore, compound 4c showed significant cell cycle disruption and apoptosis on A549 cells compared to control cells. Molecular docking of the most active compounds illustrated proper fitting to the Topo II active site, suggesting that our designed compounds are promising candidates for the development of effective anticancer agents acting through Topo II inhibition. Taylor & Francis 2023-02-12 /pmc/articles/PMC9930781/ /pubmed/36776024 http://dx.doi.org/10.1080/14756366.2023.2175209 Text en © 2023 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
El-Zoghbi, Mona S.
El-Sebaey, Samiha A.
AL-Ghulikah, Hanan A.
Sobh, Eman A.
Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title_full Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title_fullStr Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title_full_unstemmed Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title_short Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
title_sort design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase ii inhibitors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930781/
https://www.ncbi.nlm.nih.gov/pubmed/36776024
http://dx.doi.org/10.1080/14756366.2023.2175209
work_keys_str_mv AT elzoghbimonas designsynthesisdockingandanticancerevaluationsofnewthiazolo32apyrimidinesastopoisomeraseiiinhibitors
AT elsebaeysamihaa designsynthesisdockingandanticancerevaluationsofnewthiazolo32apyrimidinesastopoisomeraseiiinhibitors
AT alghulikahhanana designsynthesisdockingandanticancerevaluationsofnewthiazolo32apyrimidinesastopoisomeraseiiinhibitors
AT sobhemana designsynthesisdockingandanticancerevaluationsofnewthiazolo32apyrimidinesastopoisomeraseiiinhibitors