Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential
Abstract Obesity poses a significant global health challenge, necessitating the search for novel therapeutic agents to address this epidemic. Chromenes, known for their diverse bioactivities, hold promise as potential anti-obesity compounds, yet research in this area remains limited. This pioneering...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87945-1 |
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| author | Kewalin Inthanon Natthawut Wong-a-nan Srisulak Dheeranupattana Andres Garcia Guerra Neal M. Davies Chatchai Kesornpun Sasithorn Sangher Prasat Kittakoop |
| author_facet | Kewalin Inthanon Natthawut Wong-a-nan Srisulak Dheeranupattana Andres Garcia Guerra Neal M. Davies Chatchai Kesornpun Sasithorn Sangher Prasat Kittakoop |
| author_sort | Kewalin Inthanon |
| collection | DOAJ |
| description | Abstract Obesity poses a significant global health challenge, necessitating the search for novel therapeutic agents to address this epidemic. Chromenes, known for their diverse bioactivities, hold promise as potential anti-obesity compounds, yet research in this area remains limited. This pioneering study represents the first exploration of synthetic chromenes as potential anti-obesity agents, unveiling the underlying molecular pathways governing adipogenesis and lipolysis. Twenty-nine chromenes were synthesized using green chemistry approaches, resulting in five novel compounds: 1, 2, 3, 4, and 5. Among them, 14 chromenes demonstrated a lack of toxicity to pre-adipocytes (PAs) and mature adipocytes (MAs) of 3T3-L1 cells. The anti-adipogenesis and lipolysis enhancement potential of these non-toxic 14 chromenes were comprehensively evaluated using Oil Red O staining technique, LDH activity measurement, and glycerol release assays. Notably, 4, 5, 21 and 25 exhibited remarkable efficacy in reducing intracellular lipid accumulation without inducing cellular stress or cell death. Molecular analysis revealed significant alterations in the expression of key transcription factors involved in adipogenesis and lipid metabolism, including PPARγ, C/EBPα, ADD-1, Pref-1, IRS-1, GLUT-4, adiponectin, FAS, aP2, ATGL, and HSL. This suggests their potential role in anti-adipogenesis. Additionally, the treatments with 4 and 25 showed potential for enhancing lipolysis, providing further evidence of their anti-obesity properties. This study presents several promising prospects for the development of synthetic chromenes as potential anti-obesity agents, opening new avenues for drug discovery and benefitting individuals worldwide in addressing obesity-related challenges to human health. In addition, predictive in silico modeling was performed on the identified candidate chromenes. This modeling provides prospective anti-HIV activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these potential new chemical entities. |
| format | Article |
| id | doaj-art-865bc7e17eb3460f960eb8caeccd96b1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-865bc7e17eb3460f960eb8caeccd96b12025-02-09T12:34:05ZengNature PortfolioScientific Reports2045-23222025-02-0115112510.1038/s41598-025-87945-1Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potentialKewalin Inthanon0Natthawut Wong-a-nan1Srisulak Dheeranupattana2Andres Garcia Guerra3Neal M. Davies4Chatchai Kesornpun5Sasithorn Sangher6Prasat Kittakoop7Department of Biotechnology, Faculty Science and Technology, Thammasat University Lampang CampusDepartment of Clinical Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol UniversityDepartment of Biology, Faculty of Science, Chiang Mai UniversityFaculty of Pharmacy and Pharmaceutical Sciences, University of AlbertaFaculty of Pharmacy and Pharmaceutical Sciences, University of AlbertaFuture Biomanufacturing Research Hub (FBRH), Manchester Institute of Biotechnology, Department of Chemistry, School of Natural Science, The University of ManchesterChulabhorn Research InstituteChulabhorn Research InstituteAbstract Obesity poses a significant global health challenge, necessitating the search for novel therapeutic agents to address this epidemic. Chromenes, known for their diverse bioactivities, hold promise as potential anti-obesity compounds, yet research in this area remains limited. This pioneering study represents the first exploration of synthetic chromenes as potential anti-obesity agents, unveiling the underlying molecular pathways governing adipogenesis and lipolysis. Twenty-nine chromenes were synthesized using green chemistry approaches, resulting in five novel compounds: 1, 2, 3, 4, and 5. Among them, 14 chromenes demonstrated a lack of toxicity to pre-adipocytes (PAs) and mature adipocytes (MAs) of 3T3-L1 cells. The anti-adipogenesis and lipolysis enhancement potential of these non-toxic 14 chromenes were comprehensively evaluated using Oil Red O staining technique, LDH activity measurement, and glycerol release assays. Notably, 4, 5, 21 and 25 exhibited remarkable efficacy in reducing intracellular lipid accumulation without inducing cellular stress or cell death. Molecular analysis revealed significant alterations in the expression of key transcription factors involved in adipogenesis and lipid metabolism, including PPARγ, C/EBPα, ADD-1, Pref-1, IRS-1, GLUT-4, adiponectin, FAS, aP2, ATGL, and HSL. This suggests their potential role in anti-adipogenesis. Additionally, the treatments with 4 and 25 showed potential for enhancing lipolysis, providing further evidence of their anti-obesity properties. This study presents several promising prospects for the development of synthetic chromenes as potential anti-obesity agents, opening new avenues for drug discovery and benefitting individuals worldwide in addressing obesity-related challenges to human health. In addition, predictive in silico modeling was performed on the identified candidate chromenes. This modeling provides prospective anti-HIV activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these potential new chemical entities.https://doi.org/10.1038/s41598-025-87945-1ChromeneAnti-obesity agentAdipogenesisLipolysis3T3-L1Adipocyte |
| spellingShingle | Kewalin Inthanon Natthawut Wong-a-nan Srisulak Dheeranupattana Andres Garcia Guerra Neal M. Davies Chatchai Kesornpun Sasithorn Sangher Prasat Kittakoop Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential Scientific Reports Chromene Anti-obesity agent Adipogenesis Lipolysis 3T3-L1 Adipocyte |
| title | Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential |
| title_full | Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential |
| title_fullStr | Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential |
| title_full_unstemmed | Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential |
| title_short | Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential |
| title_sort | regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti obesity and broader therapeutic potential |
| topic | Chromene Anti-obesity agent Adipogenesis Lipolysis 3T3-L1 Adipocyte |
| url | https://doi.org/10.1038/s41598-025-87945-1 |
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