Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives
The title compounds were synthesized by the reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with various aldehydes bearing aromatic and heterocyclic moieties and acetophenones, and their cytotoxicity was tested via MTT assay against human triple-negative breast cancer MDA-MB-...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/16804 |
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| author | Irma Zubrickė Ilona Jonuškienė Kristina Kantminienė Ingrida Tumosienė Vilma Petrikaitė |
| author_facet | Irma Zubrickė Ilona Jonuškienė Kristina Kantminienė Ingrida Tumosienė Vilma Petrikaitė |
| author_sort | Irma Zubrickė |
| collection | DOAJ |
| description | The title compounds were synthesized by the reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with various aldehydes bearing aromatic and heterocyclic moieties and acetophenones, and their cytotoxicity was tested via MTT assay against human triple-negative breast cancer MDA-MB-231, human melanoma IGR39, human pancreatic carcinoma Panc-1, and prostate cancer cell line PPC-1. Furthermore, the selectivity of compounds towards cancer cells compared to fibroblasts was also investigated. Four compounds were identified as the most promising anticancer agents out of a series of pyrrolidinone-hydrazone derivatives bearing a diphenylamine moiety. These compounds were most selective against the prostate cancer cell line PPC-1 and the melanoma cell lines IGR39, with EC<sub>50</sub> values in the range of 2.5–20.2 µM against these cell lines. In general, the compounds were less active against triple-negative breast cancer MDA-MB-231 cell line, and none of them showed an inhibitory effect on the migration of these cells. In the ‘wound healing’ assay, <i>N</i>′-((5-nitrothiophen-2-yl)methylene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide was identified as the most promising derivative that could be further developed as an antimetastatic agent. <i>N</i>′-(5-chloro- and <i>N</i>′-(3,4-dichlorobenzylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazides most efficiently reduced the cell viability in IGR39 cell spheroids, while there was no effect of the investigated pyrrolidinone-hydrazone derivatives on PPC-1 3D cell cultures. Antioxidant activity determined via FRAP assay of <i>N</i>′-(1-(4-aminophenyl)ethylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide was 1.2 times higher than that of protocatechuic acid. |
| first_indexed | 2024-03-09T01:49:34Z |
| format | Article |
| id | doaj.art-1061b754a9984d3d93ff1360f3968864 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:49:34Z |
| publishDate | 2023-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1061b754a9984d3d93ff1360f39688642023-12-08T15:17:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231680410.3390/ijms242316804Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone DerivativesIrma Zubrickė0Ilona Jonuškienė1Kristina Kantminienė2Ingrida Tumosienė3Vilma Petrikaitė4Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, LithuaniaDepartment of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, LithuaniaDepartment of Physical and Inorganic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, LithuaniaDepartment of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, LithuaniaLaboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių pr. 13, 50162 Kaunas, LithuaniaThe title compounds were synthesized by the reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with various aldehydes bearing aromatic and heterocyclic moieties and acetophenones, and their cytotoxicity was tested via MTT assay against human triple-negative breast cancer MDA-MB-231, human melanoma IGR39, human pancreatic carcinoma Panc-1, and prostate cancer cell line PPC-1. Furthermore, the selectivity of compounds towards cancer cells compared to fibroblasts was also investigated. Four compounds were identified as the most promising anticancer agents out of a series of pyrrolidinone-hydrazone derivatives bearing a diphenylamine moiety. These compounds were most selective against the prostate cancer cell line PPC-1 and the melanoma cell lines IGR39, with EC<sub>50</sub> values in the range of 2.5–20.2 µM against these cell lines. In general, the compounds were less active against triple-negative breast cancer MDA-MB-231 cell line, and none of them showed an inhibitory effect on the migration of these cells. In the ‘wound healing’ assay, <i>N</i>′-((5-nitrothiophen-2-yl)methylene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide was identified as the most promising derivative that could be further developed as an antimetastatic agent. <i>N</i>′-(5-chloro- and <i>N</i>′-(3,4-dichlorobenzylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazides most efficiently reduced the cell viability in IGR39 cell spheroids, while there was no effect of the investigated pyrrolidinone-hydrazone derivatives on PPC-1 3D cell cultures. Antioxidant activity determined via FRAP assay of <i>N</i>′-(1-(4-aminophenyl)ethylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide was 1.2 times higher than that of protocatechuic acid.https://www.mdpi.com/1422-0067/24/23/16804diphenylaminepyrrolidin-2-onemelanomaprostate tumortriple-negative breast cancerpancreatic tumor |
| spellingShingle | Irma Zubrickė Ilona Jonuškienė Kristina Kantminienė Ingrida Tumosienė Vilma Petrikaitė Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives International Journal of Molecular Sciences diphenylamine pyrrolidin-2-one melanoma prostate tumor triple-negative breast cancer pancreatic tumor |
| title | Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives |
| title_full | Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives |
| title_fullStr | Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives |
| title_full_unstemmed | Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives |
| title_short | Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives |
| title_sort | synthesis and in vitro evaluation as potential anticancer and antioxidant agents of diphenylamine pyrrolidin 2 one hydrazone derivatives |
| topic | diphenylamine pyrrolidin-2-one melanoma prostate tumor triple-negative breast cancer pancreatic tumor |
| url | https://www.mdpi.com/1422-0067/24/23/16804 |
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