Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation

Neuroinflammation is considered a significant factor in triggering numerous neurodegenerative diseases. Hence, the development of effective anti-inflammatory drugs is of utmost urgency. In this study, three series of new isatin–chalcone hybrid derivatives were successfully designed and synthesized,...

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Main Authors: Rongrong Wang, Zhili Zhang, Wei Jiang, Junyi Liu, Chao Tian, Meng Wang
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/7/1421
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author Rongrong Wang
Zhili Zhang
Wei Jiang
Junyi Liu
Chao Tian
Meng Wang
author_facet Rongrong Wang
Zhili Zhang
Wei Jiang
Junyi Liu
Chao Tian
Meng Wang
author_sort Rongrong Wang
collection DOAJ
description Neuroinflammation is considered a significant factor in triggering numerous neurodegenerative diseases. Hence, the development of effective anti-inflammatory drugs is of utmost urgency. In this study, three series of new isatin–chalcone hybrid derivatives were successfully designed and synthesized, and their anti-neuritis activities were explored using BV2 microglial cells. The results indicated that compound <b>4b</b> exhibited the most potent anti-inflammatory activity (IC<sub>50</sub> = 1.6 μM; TI = 21.6). After being treated with compound <b>4b</b>, the production of TNF-α and IL-6 decreased significantly (<i>p</i> < 0.0001). <i>In silico</i> molecular modeling studies on inflammation proteins suggested that compound <b>4b</b> might bind to TLR4/MD2 and p38. Predicted by the software Molinspiration, the Log <i>p</i> value and Log BB of compound <b>4b</b> were 3.36 and −0.32, respectively.
format Article
id doaj-art-bb69382f1d0b422fa785d0bdecd06644
institution DOAJ
issn 1420-3049
language English
publishDate 2025-03-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj-art-bb69382f1d0b422fa785d0bdecd066442025-08-20T03:08:55ZengMDPI AGMolecules1420-30492025-03-01307142110.3390/molecules30071421Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity EvaluationRongrong Wang0Zhili Zhang1Wei Jiang2Junyi Liu3Chao Tian4Meng Wang5College of Pharmacy, Beihua University, Jilin 132013, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaCollege of Pharmacy, Beihua University, Jilin 132013, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaCollege of Pharmacy, Beihua University, Jilin 132013, ChinaNeuroinflammation is considered a significant factor in triggering numerous neurodegenerative diseases. Hence, the development of effective anti-inflammatory drugs is of utmost urgency. In this study, three series of new isatin–chalcone hybrid derivatives were successfully designed and synthesized, and their anti-neuritis activities were explored using BV2 microglial cells. The results indicated that compound <b>4b</b> exhibited the most potent anti-inflammatory activity (IC<sub>50</sub> = 1.6 μM; TI = 21.6). After being treated with compound <b>4b</b>, the production of TNF-α and IL-6 decreased significantly (<i>p</i> < 0.0001). <i>In silico</i> molecular modeling studies on inflammation proteins suggested that compound <b>4b</b> might bind to TLR4/MD2 and p38. Predicted by the software Molinspiration, the Log <i>p</i> value and Log BB of compound <b>4b</b> were 3.36 and −0.32, respectively.https://www.mdpi.com/1420-3049/30/7/1421anti-neuroinflammatoryisatinnitric oxideTNF-αIL-6
spellingShingle Rongrong Wang
Zhili Zhang
Wei Jiang
Junyi Liu
Chao Tian
Meng Wang
Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
Molecules
anti-neuroinflammatory
isatin
nitric oxide
TNF-α
IL-6
title Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
title_full Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
title_fullStr Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
title_full_unstemmed Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
title_short Novel Isatin–Chalcone Hybrid Molecules: Design, Synthesis and Anti-Neuroinflammatory Activity Evaluation
title_sort novel isatin chalcone hybrid molecules design synthesis and anti neuroinflammatory activity evaluation
topic anti-neuroinflammatory
isatin
nitric oxide
TNF-α
IL-6
url https://www.mdpi.com/1420-3049/30/7/1421
work_keys_str_mv AT rongrongwang novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation
AT zhilizhang novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation
AT weijiang novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation
AT junyiliu novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation
AT chaotian novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation
AT mengwang novelisatinchalconehybridmoleculesdesignsynthesisandantineuroinflammatoryactivityevaluation