| Title |
Synthesis and in vitro evaluation as potential anticancer and antioxidant agents of diphenylamine-pyrrolidin-2-one-hydrazone derivatives / |
| Authors |
Zubrickė, Irma ; Jonuškienė, Ilona ; Kantminienė, Kristina ; Tumosienė, Ingrida ; Petrikaitė, Vilma |
| DOI |
10.3390/ijms242316804 |
| Full Text |
|
| Is Part of |
International journal of molecular sciences.. Basel : MDPI. 2023, vol. 24, iss. 23, art. no. 16804, p. 1-19.. ISSN 1661-6596. eISSN 1422-0067 |
| Keywords [eng] |
diphenylamine ; pyrrolidin-2-one ; melanoma ; prostate tumor ; triple-negative breast cancer ; pancreatic tumor ; 3D tumor model ; migration ; antioxidative ; FRAP |
| Abstract [eng] |
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 EC50 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, N′-((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. N′-(5-chloro- and N′-(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 N′-(1-(4-aminophenyl)ethylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide was 1.2 times higher than that of protocatechuic acid. |
| Published |
Basel : MDPI |
| Type |
Journal article |
| Language |
English |
| Publication date |
2023 |
| CC license |
|
