Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives
(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Th...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7925 |
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| author | Lin-Hao Zhang Ming-Yue Li Da-Yuan Wang Xue-Jun Jin Fen-Er Chen Hu-Ri Piao |
| author_facet | Lin-Hao Zhang Ming-Yue Li Da-Yuan Wang Xue-Jun Jin Fen-Er Chen Hu-Ri Piao |
| author_sort | Lin-Hao Zhang |
| collection | DOAJ |
| description | (1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound <b>6d</b> exhibited the most promising inhibitory activity (IC<sub>50</sub> = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that <b>6d</b> down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound <b>4f</b> was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds <b>6d</b> and <b>4f</b> had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents. |
| first_indexed | 2024-03-09T18:07:25Z |
| format | Article |
| id | doaj.art-dd181d8160c543dc873fd1cef83853d3 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:07:25Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-dd181d8160c543dc873fd1cef83853d32023-11-24T09:23:29ZengMDPI AGMolecules1420-30492022-11-012722792510.3390/molecules27227925Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin DerivativesLin-Hao Zhang0Ming-Yue Li1Da-Yuan Wang2Xue-Jun Jin3Fen-Er Chen4Hu-Ri Piao5Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, China(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound <b>6d</b> exhibited the most promising inhibitory activity (IC<sub>50</sub> = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that <b>6d</b> down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound <b>4f</b> was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds <b>6d</b> and <b>4f</b> had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.https://www.mdpi.com/1420-3049/27/22/7925molluginNF-κB inhibitoranti-inflammatory activitycytotoxicityADMET |
| spellingShingle | Lin-Hao Zhang Ming-Yue Li Da-Yuan Wang Xue-Jun Jin Fen-Er Chen Hu-Ri Piao Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives Molecules mollugin NF-κB inhibitor anti-inflammatory activity cytotoxicity ADMET |
| title | Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives |
| title_full | Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives |
| title_fullStr | Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives |
| title_full_unstemmed | Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives |
| title_short | Synthesis and Evaluation of NF-κB Inhibitory Activity of Mollugin Derivatives |
| title_sort | synthesis and evaluation of nf κb inhibitory activity of mollugin derivatives |
| topic | mollugin NF-κB inhibitor anti-inflammatory activity cytotoxicity ADMET |
| url | https://www.mdpi.com/1420-3049/27/22/7925 |
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