biostudies-literatureSong JQGuangdong Provincial Department of Science and TechnologyDouble First-Class Project of China Pharmaceutical University2024 Guangdong Pharmaceutical University's "Discipline Training Excellence, Innovation and Quality Improvement" Engineering Team ProjectDepartment of Science and Technology of Guangdong ProvinceNatural Medicines of China Pharmaceutical UniversityTop Talent Support Program for Young and Middle-aged People of Wuxi Health CommitteeNational Natural Science Foundation of ChinaOpen Project of Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education of Hainan Medical Universitye2410550https://www.ebi.ac.uk/biostudies/studies/S-EPMC11672292biostudies-literatureUnknown11(48)Macrophage-mediated inflammatory responses including pyroptosis are involved in the pathogenesis of sepsis and acute lung injury (ALI), for which there are currently no effective therapeutic treatments. The natural product (+)-Balasubramide is an eight-membered lactam compound extracted from the leaves of the Sri Lanka plant Clausena Indica and has shown anti-inflammatory activities, but its poor pharmacokinetic properties limit its further application for ALI. In this study, a compound (+)3C-20 is discovered with improved both pharmacokinetic properties and anti-inflammatory activity from a series of (+)-Balasubramide derivatives. The compound (+)3C-20 exhibits a markedly enhanced inhibitory effect against LPS-induced expressions of pro-inflammatory factors in mouse macrophages and human Advanced science (Weinheim, Baden-Wurttemberg, Germany)Discovery of Balasubramide Derivative with Tissue-Specific Anti-Inflammatory Activity Against Acute Lung Injury by Targeting VDAC1.PMC116722922015A020211031No.2024ZZ05Grant No. TMIT2024Z03CPUQNJC22_022016A020217022No. BJ2023066822051108197351282174010SKLNMKF202405Cai BLin HSPang TShi LLiu KLiu QBSong JQShen LJWang HJYe LBfalseDiscovery of Balasubramide Derivative with Tissue-Specific Anti-Inflammatory Activity Against Acute Lung Injury by Targeting VDAC1.Macrophage-mediated inflammatory responses including pyroptosis are involved in the pathogenesis of sepsis and acute lung injury (ALI), for which there are currently no effective therapeutic treatments. The natural product (+)-Balasubramide is an eight-membered lactam compound extracted from the leaves of the Sri Lanka plant Clausena Indica and has shown anti-inflammatory activities, but its poor pharmacokinetic properties limit its further application for ALI. In this study, a compound (+)3C-20 is discovered with improved both pharmacokinetic properties and anti-inflammatory activity from a series of (+)-Balasubramide derivatives. The compound (+)3C-20 exhibits a markedly enhanced inhibitory effect against LPS-induced expressions of pro-inflammatory factors in mouse macrophages and human 2024-01-01T00:00:00Z2024 Dec2026-06-01T20:04:26.296Z2025-04-19T21:26:34.019ZS-EPMC116722923955671310.1002/advs.202410550