Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives

Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Co...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Paulina Strzyga-Łach, Alicja Chrzanowska, Katarzyna Podsadni, Anna Bielenica
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	thiourea cytotoxic activity apoptosis interleukin-6 trypan blue assay Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/c7197d877528405aa0fda44bf124f5f6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c7197d877528405aa0fda44bf124f5f6
record_format	dspace
spelling	oai:doaj.org-article:c7197d877528405aa0fda44bf124f5f62021-11-25T18:39:19ZInvestigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives10.3390/ph141110971424-8247https://doaj.org/article/c7197d877528405aa0fda44bf124f5f62021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1097https://doaj.org/toc/1424-8247Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Compounds <b>1</b>–<b>5</b>, <b>8</b>, and <b>9</b> were highly cytotoxic against human colon (SW480, SW620) and prostate (PC3) cancer cells, and leukemia K-562 cell lines (IC<sub>50</sub> ≤ 10 µM), with favorable selectivity over normal HaCaT cells. The derivatives exerted better growth inhibitory profiles towards selected tumor cells than the reference cisplatin. Compounds incorporating 3,4-dichloro- (<b>2</b>) and 4-CF<sub>3</sub>-phenyl (<b>8</b>) substituents displayed the highest activity (IC<sub>50</sub> from 1.5 to 8.9 µM). The mechanisms of cytotoxic action of the most effective thioureas <b>1</b>–<b>3</b>, <b>8</b>, and <b>9</b> were studied, including the trypan blue exclusion test of cell viability, interleukin-6, and apoptosis assessments. Compounds reduced all cancerous cell numbers (especially SW480 and SW620) by 20–93%. Derivatives <b>2</b> and <b>8</b> diminished the viability of SW620 cells by 45–58%. Thioureas <b>1</b>, <b>2</b>, and <b>8</b> exerted strong pro-apoptotic activity. Compound <b>2</b> induced late apoptosis in both colon cancer cell lines (95–99%) and in K-562 cells (73%). All derivatives acted as inhibitors of IL-6 levels in both SW480 and SW620 cells, decreasing its secretion by 23–63%.Paulina Strzyga-ŁachAlicja ChrzanowskaKatarzyna PodsadniAnna BielenicaMDPI AGarticlethioureacytotoxic activityapoptosisinterleukin-6trypan blue assayMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1097, p 1097 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thiourea cytotoxic activity apoptosis interleukin-6 trypan blue assay Medicine R Pharmacy and materia medica RS1-441
spellingShingle	thiourea cytotoxic activity apoptosis interleukin-6 trypan blue assay Medicine R Pharmacy and materia medica RS1-441 Paulina Strzyga-Łach Alicja Chrzanowska Katarzyna Podsadni Anna Bielenica Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
description	Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Compounds <b>1</b>–<b>5</b>, <b>8</b>, and <b>9</b> were highly cytotoxic against human colon (SW480, SW620) and prostate (PC3) cancer cells, and leukemia K-562 cell lines (IC<sub>50</sub> ≤ 10 µM), with favorable selectivity over normal HaCaT cells. The derivatives exerted better growth inhibitory profiles towards selected tumor cells than the reference cisplatin. Compounds incorporating 3,4-dichloro- (<b>2</b>) and 4-CF<sub>3</sub>-phenyl (<b>8</b>) substituents displayed the highest activity (IC<sub>50</sub> from 1.5 to 8.9 µM). The mechanisms of cytotoxic action of the most effective thioureas <b>1</b>–<b>3</b>, <b>8</b>, and <b>9</b> were studied, including the trypan blue exclusion test of cell viability, interleukin-6, and apoptosis assessments. Compounds reduced all cancerous cell numbers (especially SW480 and SW620) by 20–93%. Derivatives <b>2</b> and <b>8</b> diminished the viability of SW620 cells by 45–58%. Thioureas <b>1</b>, <b>2</b>, and <b>8</b> exerted strong pro-apoptotic activity. Compound <b>2</b> induced late apoptosis in both colon cancer cell lines (95–99%) and in K-562 cells (73%). All derivatives acted as inhibitors of IL-6 levels in both SW480 and SW620 cells, decreasing its secretion by 23–63%.
format	article
author	Paulina Strzyga-Łach Alicja Chrzanowska Katarzyna Podsadni Anna Bielenica
author_facet	Paulina Strzyga-Łach Alicja Chrzanowska Katarzyna Podsadni Anna Bielenica
author_sort	Paulina Strzyga-Łach
title	Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
title_short	Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
title_full	Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
title_fullStr	Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
title_full_unstemmed	Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
title_sort	investigation of the mechanisms of cytotoxic activity of 1,3-disubstituted thiourea derivatives
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c7197d877528405aa0fda44bf124f5f6
work_keys_str_mv	AT paulinastrzygałach investigationofthemechanismsofcytotoxicactivityof13disubstitutedthioureaderivatives AT alicjachrzanowska investigationofthemechanismsofcytotoxicactivityof13disubstitutedthioureaderivatives AT katarzynapodsadni investigationofthemechanismsofcytotoxicactivityof13disubstitutedthioureaderivatives AT annabielenica investigationofthemechanismsofcytotoxicactivityof13disubstitutedthioureaderivatives
_version_	1718410862405877760

Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives

Ejemplares similares