Title The effect of 4-(dimethylamino)phenyl-5-oxopyrrolidines on breast and pancreatic cancer cell colony formation, migration, and growth of tumor spheroids /
Authors Kairytė, Karolina ; Vaickelionienė, Rita ; Grybaitė, Birutė ; Anusevičius, Kazimieras ; Mickevičius, Vytautas ; Petrikaitė, Vilma
DOI 10.3390/ijms25031834
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Is Part of International journal of molecular sciences.. Basel : MDPI. 2024, vol. 25, iss. 3, art. no. 1834, p. 1-23.. ISSN 1661-6596. eISSN 1422-0067
Keywords [eng] triple-negative breast cancer ; pancreatic cancer ; cell viability ; cell migration ; clonogenic assay ; tumor spheroid
Abstract [eng] A series of hydrazones, azoles, and azines bearing a 4-dimethylaminophenyl-5-oxopyrrolidine scaffold was synthesized. Their cytotoxic effect against human pancreatic carcinoma Panc-1 and triple-negative breast cancer MDA-MB-231 cell lines was established by MTT assay. Pyrrolidinone derivatives 3c and 3d, with incorporated 5-chloro and 5-methylbenzimidazole fragments; hydrazone 5k bearing a 5-nitrothien-2-yl substitution; and hydrazone 5l with a naphth-1-yl fragment in the structure significantly decreased the viability of both cancer cell lines. Compounds 3c and 5k showed the highest selectivity, especially against the MDA-MB-231 cancer cell line. The EC50 values of the most active compound 5k against the MDA-MB231 cell line was 7.3 ± 0.4 μM, which were slightly higher against the Panc-1 cell line (10.2 ± 2.6 μM). Four selected pyrrolidone derivatives showed relatively high activity in a clonogenic assay. Compound 5k was the most active in both cell cultures, and it completely disturbed MDA-MB-231 cell colony growth at 1 and 2 μM and showed a strong effect on Panc-1 cell colony formation, especially at 2 μM. The compounds did not show an inhibitory effect on cell line migration by the ‘wound-healing’ assay. Compound 3d most efficiently inhibited the growth of Panc-1 spheroids and reduced cell viability in MDA-MB-231 spheroids. Considering these different activities in biological assays, the selected pyrrolidinone derivatives could be further tested to better understand the structure–activity relationship and their mechanism of action.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2024
CC license CC license description