The Effect of 4-(Dimethylamino)phenyl-5-oxopyrrolidines on Breast and Pancreatic Cancer Cell Colony Formation, Migration, and Growth of Tumor Spheroids
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 <b...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/3/1834 |
| Summary: | 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 <b>3c</b> and <b>3d</b>, with incorporated 5-chloro and 5-methylbenzimidazole fragments; hydrazone <b>5k</b> bearing a 5-nitrothien-2-yl substitution; and hydrazone <b>5l</b> with a naphth-1-yl fragment in the structure significantly decreased the viability of both cancer cell lines. Compounds <b>3c</b> and <b>5k</b> showed the highest selectivity, especially against the MDA-MB-231 cancer cell line. The EC<sub>50</sub> values of the most active compound <b>5k</b> 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 <b>5k</b> 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 <b>3d</b> 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. |
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| ISSN: | 1661-6596 1422-0067 |