{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T22:53:59Z","timestamp":1773183239235,"version":"3.50.1"},"reference-count":114,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.<\/jats:p>","DOI":"10.3390\/molecules25030493","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:41:57Z","timestamp":1580125317000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Biological Activities of Gedunin\u2014A Limonoid from the Meliaceae Family"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1067-9419","authenticated-orcid":false,"given":"Teresa M.","family":"Braga","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-2386","authenticated-orcid":false,"given":"L\u00eddia","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"given":"Tsz Yan","family":"Chung","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"given":"Rita F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"given":"Cl\u00e1udia","family":"Pinho","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-6476","authenticated-orcid":false,"given":"Ana I.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"given":"Joaquim","family":"Morgado","sequence":"additional","affiliation":[{"name":"Bio4Life4You, 4460-170 Porto, Portugal"},{"name":"World Neem Organization, Mumbai 400101, India"}]},{"given":"Agostinho","family":"Cruz","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade e Ambiente, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.tifs.2018.10.001","article-title":"Selected commercial plants: A review of extraction and isolation of bioactive compounds and their pharmacological market value","volume":"82","author":"Patra","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bjp.2014.11.009","article-title":"Phytochemicals and antimicrobial potentials of mahogany family","volume":"25","author":"Paritala","year":"2015","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1248\/bpb.29.191","article-title":"Limonoids: Overview of significant bioactive triterpenes distributed in plants kingdom","volume":"29","author":"Roy","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1021\/cr9004023","article-title":"Meliaceous limonoids: Chemistry and biological activities","volume":"111","author":"Tan","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/ptr.2159","article-title":"Gedunin, a limonoid from Xylocarpus granatum, inhibits the growth of CaCo-2 colon cancer cell line in vitro","volume":"21","author":"Uddin","year":"2007","journal-title":"Phyther. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molstruc.2011.11.028","article-title":"X-ray diffraction and theoretical investigation of the gedunin crystal structure","volume":"1008","author":"Carvalho","year":"2012","journal-title":"J. Mol. Struct."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s10812-016-0379-x","article-title":"The applied validated ultraviolet-visible spectrophotometric method and the kinetic model of the release of gedunin from a chitosan-coated liposome","volume":"83","author":"Sahu","year":"2016","journal-title":"J. Appl. Spectrosc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.crci.2003.12.032","article-title":"\u00c9valuation de la teneur en g\u00e9dunine dans diff\u00e9rents organes d\u2019Azadirachta indica A. Juss","volume":"7","author":"Koumaglo","year":"2004","journal-title":"Comptes Rendus Chim."},{"key":"ref_9","first-page":"1336","article-title":"Biological activities and medicinal properties of neem (Azadirachta indica)","volume":"82","author":"Biswas","year":"2002","journal-title":"Curr. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.phytol.2012.04.011","article-title":"Fluorinated and rearranged gedunin derivatives","volume":"5","author":"Hitotsuyanagi","year":"2012","journal-title":"Phytochem. Lett."},{"key":"ref_11","first-page":"131","article-title":"Neem limonoids as anticancer agents: Modulation of cancer hallmarks and oncogenic signaling","volume":"Volume 36","author":"Bathaie","year":"2014","journal-title":"Enzymes. Natural Products and Cancer Signaling: Isoprenoids, Polyphenols and Flavonoids"},{"key":"ref_12","first-page":"203","article-title":"Occurrence, biosynthesis, biological activity and NMR spectroscopy of D and B, D ring seco-limonoids of Meliaceae family","volume":"2","author":"Narender","year":"2007","journal-title":"Nat. Prod. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Akhila, A., and Rani, K. (1999). Chemistry of the neem tree (Azadirachta indica A. Juss.). Progress in the Chemistry of Organic Natural Products, Springer.","DOI":"10.1007\/978-3-7091-6394-8_2"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1021\/jf990443q","article-title":"Growth inhibitory effects on fall armyworm Spodoptera frugiperda of some limonoids isolated from Cedrela spp. (Meliaceae)","volume":"48","author":"Lina","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12870-018-1447-6","article-title":"Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension","volume":"18","author":"Aarthy","year":"2018","journal-title":"BMC Plant Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Akisanya, A., Bevan, C.W.L., Hirst, J., Halsall, T.G., and Taylor, D.A.H. (1960). 758. West African timbers. Part III. Petroleum extracts from the genus Entandrophragma. J. Chem. Soc., 506\u2013509.","DOI":"10.1039\/jr9600003827"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Akisanya, A., Bevan, C.W.L., Halsall, T.G., Powell, J.W., and Taylor, D.A.H. (1961). 720. West African timbers. Part IV. Some reactions of gedunin. J. Chem. Soc., 3705\u20133708.","DOI":"10.1039\/jr9610003705"},{"key":"ref_18","unstructured":"Sutherland, S.A., Sim, G.A., and Robertson, J.M. (1962). Structure of gedunin. Proc. Chem. Soc. Lond., 222\u2013224."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Powell, J.W. (1966). Nuclear magnetic resonance spectroscopy, the bandwidths of the singlets in gedunin and its simple derivatives. Chem. Commun., 422\u2013423.","DOI":"10.1039\/c19660000422"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Baldwin, M.A., Loudon, A.G., Maccoll, A., and Bevan, C.W.L. (1967). The mass spectra of meliacins and related compounds. Part I. Gedunin and related compounds. J. Chem. Soc. C Org. Chem., 1026\u20131034.","DOI":"10.1039\/j39670001026"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01991968","article-title":"Gedunin, a D-seco limonoid","volume":"26","author":"Toscano","year":"1996","journal-title":"J. Chem. Crystallogr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1021\/np9605394","article-title":"Antimalarial activity of tropical Meliaceae extracts and gedunin derivatives","volume":"60","author":"MacKinnon","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1744-7348.2003.tb00279.x","article-title":"Antimalarial activities of gedunin and 7-methoxygedunin and synergistic activity with dillapiol","volume":"143","author":"Omar","year":"2003","journal-title":"Ann. Appl. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6495","DOI":"10.1021\/jm8007486","article-title":"Gedunin, a novel hsp90 inhibitor: Semisynthesis of derivatives and preliminary structure-activity relationships","volume":"51","author":"Brandt","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1002\/chem.201605751","article-title":"Gaining synthetic appreciation for the gedunin ABC ring system","volume":"23","author":"Pinkerton","year":"2017","journal-title":"Chem. A Eur. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ajoc.201700013","article-title":"Towards the total synthesis of gedunin: Construction of the fully elaborated ABC ring system","volume":"6","author":"Pinkerton","year":"2017","journal-title":"Asian J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/chem.201805420","article-title":"Synthesis of the seco-limonoid BCD ring system identifies a Hsp90 chaperon machinery (p23) inhibitor","volume":"25","author":"Pinkerton","year":"2019","journal-title":"Chem. A Eur. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1111\/IGC.0b013e3181a83135","article-title":"Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation","volume":"19","author":"Kamath","year":"2009","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Johnson, J., Venugopal, A., Kwatra, D., Roby, K., Godwin, A., and Anant, S. (2014, January 5\u20139). Gedunin, a novel HSP-90 inhibitor, synergizes with cisplatin and paclitaxel to inhibit growth of chemoresistant ovarian cancer cell lines. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research, San Diego, CA, USA.","DOI":"10.1158\/1538-7445.AM2014-4553"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.1074\/jbc.M112.427328","article-title":"Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis","volume":"288","author":"Patwardhan","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2174\/187152010794728620","article-title":"Evaluation of effect of triterpenes and limonoids on cell growth, cell cycle and apoptosis in human tumor cell lines","volume":"10","author":"Cazal","year":"2010","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/cbdv.201300406","article-title":"Limonoids from Azadirachta indica var. siamensis extracts and their cytotoxic and melanogenesis-inhibitory activities","volume":"11","author":"Manosroi","year":"2014","journal-title":"Chem. Biodivers."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1021\/np100783k","article-title":"Cytotoxic and apoptosis-inducing activities of limonoids from the seeds of Azadirachta indica (Neem)","volume":"74","author":"Kikuchi","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s13277-015-4003-0","article-title":"Gedunin abrogates aldose reductase, PI3K\/Akt\/mToR, and NF-\u03baB signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis","volume":"37","author":"Kishore","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.2174\/1871520618666180731093433","article-title":"Gedunin, a neem limonoid in combination with epalrestat inhibits cancer hallmarks by attenuating aldose reductase-driven oncogenic signaling in SCC131 oral cancer cells","volume":"18","author":"Tanagala","year":"2018","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10891","DOI":"10.18632\/oncotarget.8055","article-title":"Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway","volume":"8","author":"Subramani","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccr.2006.09.005","article-title":"Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators","volume":"10","author":"Hieronymus","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_39","unstructured":"Boopalan, T., Chaudhary, A., Murali, S., Arumugam, A., Lopez, R., Nandy, S., Gutierrez, C., Parada, J., Agullo, P., and Lakshmanaswamy, R. (2013, January 6\u201310). Anticancer effect of gedunin against pancreatic cancer cell lines. Proceedings of the 104th AACR Annual Meeting 2013, Washington, DC, USA."},{"key":"ref_40","first-page":"25","article-title":"PI3K\/AKT Pathway is inhibited in NSCLC cell line A549 by downregulation of EGFR via an HSP-90 inhibitor Gedunin","volume":"7","author":"Hasan","year":"2018","journal-title":"Cancer Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.4314\/tjpr.v16i9.6","article-title":"Induction of apoptosis in response to improved gedunin by liposomal nano-encapsulation in human non-small-cell lung cancer (NCI-H292) cell line","volume":"16","author":"Nwokwu","year":"2017","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"522","DOI":"10.3923\/ijp.2018.522.527","article-title":"Inhibition of proliferation, invasion and migration in U-251 MG glioblastoma cell line by gedunin","volume":"14","author":"Li","year":"2018","journal-title":"Int. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.fitote.2013.07.001","article-title":"Andirolides Q\u2013V from the flower of andiroba (Carapa guianensis, Meliaceae)","volume":"90","author":"Sakamoto","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"581","DOI":"10.5650\/jos.58.581","article-title":"Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indicia A. Juss. (Neem)","volume":"594","author":"Akihisa","year":"2009","journal-title":"J. Oleo Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tharmarajah, L., Samarakoon, S.R., Ediriweera, M.K., Piyathilaka, P., Tennekoon, K.H., Senathilake, K.S., Rajagopalan, U., Galhena, P.B., and Thabrew, I. (2017). In vitro anticancer effect of gedunin on human teratocarcinomal (NTERA-2) cancer stem-like cells. Biomed Res. Int., 2017.","DOI":"10.1155\/2017\/2413197"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1055\/s-0035-1546251","article-title":"Hsp90 activity modulation by plant secondary metabolites","volume":"81","author":"Piaz","year":"2015","journal-title":"Planta Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejmech.2019.05.073","article-title":"Inhibiting protein-protein interactions of Hsp90 as a novel approach for targeting cancer","volume":"178","author":"Bommaka","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bmc.2010.10.029","article-title":"A systematic protocol for the characterization of Hsp90 modulators","volume":"19","author":"Matts","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Moga, M.A., B\u0103lan, A., Anastasiu, C.V., Dimienescu, O.G., Neculoiu, C.D., and Gavri\u0219, C. (2018). An overview on the anticancer activity of Azadirachta indica (Neem) in gynecological cancers. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123898"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1056\/NEJMra0708126","article-title":"Malignant gliomas in adults","volume":"359","author":"Wen","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1038\/480S43a","article-title":"Tumorigenesis: Testing ground for cancer stem","volume":"480","author":"Delude","year":"2011","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/EJMP\/2016\/27847","article-title":"Evaluation of selected natural compounds for cancer stem cells targeted anti-cancer activity: A molecular docking study","volume":"15","author":"Mayan","year":"2016","journal-title":"Eur. J. Med. Plants"},{"key":"ref_53","first-page":"1","article-title":"The promise of neuroprotective agents in Parkinson\u2019s disease","volume":"21","author":"Seidl","year":"2011","journal-title":"Front. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1523\/JNEUROSCI.3117-15.2016","article-title":"Regulation of ATP13A2 via PHD2-HIF1 signaling is critical for cellular iron homeostasis: Implications for Parkinson\u2019s disease","volume":"36","author":"Rajagopalan","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.neuro.2018.02.012","article-title":"Hsp90 Co-chaperone p23 contributes to dopaminergic mitochondrial stress via stabilization of PHD2: Implications for Parkinson\u2019s disease","volume":"65","author":"Rane","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tom, S., Rane, A., Katewa, A.S., Chamoli, M., Matsumoto, R.R., Andersen, J.K., and Chinta, S.J. (2019). Gedunin inhibits oligomeric A\u03b21\u201342-induced microglia activation via modulation of Nrf2-NF-\u03baB signaling. Mol. Neurobiol., 1\u201312.","DOI":"10.1007\/s12035-019-1636-9"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1124\/mol.115.098970","article-title":"Gedunin binds to myeloid differentiation protein 2 and impairs lipopolysaccharide-induced toll-like receptor 4 signaling in macrophages","volume":"88","author":"Borges","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.phrs.2016.09.015","article-title":"Protective effect of gedunin on TLR-mediated inflammation by modulation of inflammasome activation and cytokine production: Evidence of a multitarget compound","volume":"115","author":"Borges","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chembiol.2011.03.013","article-title":"Development of Neh2-luciferase reporter and its application for high throughput screening and real-time monitoring of Nrf2 activators","volume":"18","author":"Smirnova","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000497580","article-title":"Diabetes mellitus and its treatment","volume":"13","author":"Bastaki","year":"2005","journal-title":"Int. J. Diabetes Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/cbic.200700470","article-title":"The search for novel human pancreatic \u03b1-amylase inhibitors: High-throughput screening of terrestrial and marine natural product extracts","volume":"9","author":"Tarling","year":"2008","journal-title":"ChemBioChem"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0140113","article-title":"Gedunin and azadiradione: Human pancreatic \u03b1-amylase inhibiting limonoids from neem (Azadirachta indica) as anti-diabetic agents","volume":"10","author":"Ponnusamy","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.intimp.2012.06.002","article-title":"Gedunin, a natural tetranortriterpenoid, modulates T lymphocyte responses and ameliorates allergic inflammation","volume":"14","author":"Ferraris","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00011-005-1357-6","article-title":"Anti-allergic effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on allergen-induced vascular permeability and hyperalgesia","volume":"54","author":"Penido","year":"2005","journal-title":"Inflamm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.intimp.2005.07.011","article-title":"Inhibition of allergen-induced eosinophil recruitment by natural tetranortriterpenoids is mediated by the suppression of IL-5, CCL11\/eotaxin and NF\u03baB activation","volume":"6","author":"Penido","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/j.chemosphere.2005.07.051","article-title":"The toxicity and behavioural effects of neem limonoids on Cnaphalocrocis medinalis (Guen\u00e9e), the rice leaffolder","volume":"62","author":"Kalaivani","year":"2006","journal-title":"Chemosphere"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1021\/bk-1986-0296.ch017","article-title":"Insect ecdysis inhibitors","volume":"Volume 296","author":"Kubo","year":"1986","journal-title":"Natural Resistance of Plants to Pests"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1515\/znc-2001-5-611","article-title":"Acetylcholinesterase and insect growth inhibitory activities of gutierrezia microcephala on fall army worm Spodoptera frugiperda J. E. Smith","volume":"56","author":"Rosas","year":"2001","journal-title":"Zeitschrift f\u00fcr Naturforschung C"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0031-9422(03)00348-0","article-title":"Antioxidant and insect growth regulatory activities of stilbenes and extracts from Yucca periculosa","volume":"64","author":"Torres","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.phytochem.2004.03.037","article-title":"Insect growth inhibition by tocotrienols and hydroquinones from Roldana barba-johannis","volume":"65","author":"Torres","year":"2004","journal-title":"Phytochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1016\/j.phytochem.2005.07.010","article-title":"Insect growth regulatory effects of some extracts and sterols from Myrtillocactus geometrizans (Cactaceae) against Spodoptera frugiperda and Tenebrio molitor","volume":"66","author":"Salazar","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.cropro.2005.01.009","article-title":"Efficacy of neem limonoids on Cnaphalocrocis medinalis (Guen\u00e9e) (Lepidoptera: Pyralidae) the rice leaffolder","volume":"24","author":"Nathan","year":"2005","journal-title":"Crop Prot."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.pestbp.2004.10.004","article-title":"The toxicity and physiological effect of neem limonoids on Cnaphalocrocis medinalis (Guen\u00e9e) the rice leaffolder","volume":"81","author":"Nathan","year":"2005","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.chemosphere.2005.07.009","article-title":"Effect of neem limonoids on lactate dehydrogenase (LDH) of the rice leaffolder, Cnaphalocrocis medinalis (Guen\u00e9e) (Insecta: Lepidoptera: Pyralidae)","volume":"62","author":"Nathan","year":"2005","journal-title":"Chemosphere"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1002\/hlca.200390277","article-title":"Transformation of azadiradione to nimbocinol and 17\u03b2-hydroxynimbocinol, and structure pesticidal-activity relationship of triterpenoids isolated from Azadirachta indica A. Juss. (Neem)","volume":"86","author":"Siddiqui","year":"2003","journal-title":"Helv. Chim. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.actatropica.2005.07.002","article-title":"Effects of neem limonoids on the malaria vector Anopheles stephensi Liston (Diptera: Culicidae)","volume":"96","author":"Nathan","year":"2005","journal-title":"Acta Trop."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1570-7458.1987.tb02213.x","article-title":"Limonoids from the Meliaceae and Rutaceae reduce feeding, growth and development of Ostrinia nubilalis","volume":"43","author":"Arnason","year":"1987","journal-title":"Entomol. Exp. Appl."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4314\/dai.v12i1.15569","article-title":"Toxicity of gedunin, piperine and crude extracts of their natural products on growth and development of Ostrinia nubilalis H\u00fcbner (Lepidoptera: Pyralidae)","volume":"12","author":"Ewete","year":"2000","journal-title":"Discov. Innov."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1271\/bbb.56.1835","article-title":"Several antifeedants from neem oil, Azadirachta indica A. Juss., against Reticulitermes speratus Kolbe (Isoptera: Rhinotermitidae)","volume":"56","author":"Ishida","year":"1992","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1584\/jpestics.17.4_267","article-title":"Antifeeding potency of neem (Azadirachta indica) extractives and limonoids against termite (Reticulitermes speratus)","volume":"17","author":"Serit","year":"1992","journal-title":"J. Pestic. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1017\/S1742758400007803","article-title":"Antifeedant and growth-inhibitory properties of neem limonoids against the cotton bollworm, Helicoverpa armigera (H\u00fcbner)","volume":"18","author":"Murugan","year":"1998","journal-title":"Int. J. Trop. Insect Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1021\/jf021049m","article-title":"6\u03b2-hydroxygedunin from Azadirachta indica. Its potentiation effects with some non-azadirachtin limonoids in neem against lepidopteran larvae","volume":"51","author":"Koul","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jspr.2005.11.005","article-title":"Antifeedant activities of terpenoids isolated from tropical Rutales","volume":"43","author":"Omar","year":"2007","journal-title":"J. Stored Prod. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/cbdv.200800105","article-title":"Susceptibility of Aedes aegypti and Culex quinquefasciatus larvae to gedunin-related limonoids","volume":"6","author":"Gurulingappa","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/1748-5967.12059","article-title":"Limonoid derivatives and its pesticidal activities","volume":"44","author":"Park","year":"2014","journal-title":"Entomol. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1515\/znc-2009-5-623","article-title":"Effects of limonoids from Cipadessa fruticosa on fall armyworm","volume":"64","author":"Matos","year":"2009","journal-title":"Zeitschrift f\u00fcr Naturforschung C"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.indcrop.2012.12.038","article-title":"Insect growth regulatory effects by diterpenes from Calceolaria talcana Grau & Ehrhart (Calceolariaceae: Scrophulariaceae) against Spodoptera frugiperda and Drosophila melanogaster","volume":"45","author":"Escalona","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.indcrop.2015.06.003","article-title":"Ceanothane and oleanane-type triterpenes from Talguenea quinquenervia have insecticidal activity against Cydia pomonella, Tenebrio molitor and Drosophila melanogaster","volume":"74","author":"Quiroz","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.indcrop.2016.05.026","article-title":"Calceolaria integrifolia s.l. complex, reduces feeding and growth of Acanthoscelides obtectus, and Epilachna varivestis. A new source of bioactive compounds against dry bean pests","volume":"89","author":"Cespedes","year":"2016","journal-title":"Ind. Crops Prod."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1351\/pac199466102347","article-title":"Biologically active constituents of tropical and subtropical plants","volume":"66","author":"Kraus","year":"1994","journal-title":"Pure Appl. Chem."},{"key":"ref_91","first-page":"17","article-title":"Phytotoxicity of triterpenes and limonoids from the Rutaceae and Meliaceae. 5\u03b1,6\u03b2,8\u03b1,12\u03b1-tetrahydro-28-norisotoonafolin\u2014A potent phytotoxin from Toona ciliata","volume":"10","author":"Nebo","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_92","first-page":"714","article-title":"Antifungal activity of gedunin","volume":"46","author":"Rao","year":"1977","journal-title":"Curr. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7815","DOI":"10.1021\/jf801103p","article-title":"Chemical characterization of Citrus sinensis grafted on C. limonia and the effect of some isolated compounds on the growth of Xylella fastidiosa","volume":"56","author":"Ribeiro","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0378-8741(86)90156-X","article-title":"Potential antimalarial candidates from African plants: An in vitro approach using Plasmodium falciparum","volume":"15","author":"Khalid","year":"1986","journal-title":"J. Ethnopharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/ptr.2650040108","article-title":"Plants as sources of antimalarial drugs. Part 7. Activity of some species of Meliaceae plants and their constituent limonoids","volume":"4","author":"Bray","year":"1990","journal-title":"Phyther. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0378-8741(99)00117-8","article-title":"In vitro antimalarial activity of limonoids from Khaya grandifoliola C.D.C. (Meliaceae)","volume":"69","author":"Bickii","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.phymed.2007.08.001","article-title":"Antimalarial activity of anthothecol derived from Khaya anthotheca (Meliaceae)","volume":"15","author":"Lee","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1021\/np100325q","article-title":"Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica","volume":"73","author":"Chianese","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1080\/14786419.2010.535000","article-title":"Antimalarial activity in Xylocarpus granatum (Koen)","volume":"26","author":"Lakshmi","year":"2012","journal-title":"Nat. Prod. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jep.2012.05.037","article-title":"Antiplasmodial activity of the andiroba (Carapa guianensis Aubl., Meliaceae) oil and its limonoid-rich fraction","volume":"142","author":"Dolabela","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"326","DOI":"10.36468\/pharmaceutical-sciences.514","article-title":"In silico docking study of limonoids from Azadirachta indica with pfpk5: A novel target for Plasmodium falciparum","volume":"81","author":"Khanal","year":"2019","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00436-011-2380-x","article-title":"Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host","volume":"109","author":"Misra","year":"2011","journal-title":"Parasitol. Res."},{"key":"ref_103","first-page":"1","article-title":"In vitro inhibitory effect of gedunin on Babesia and Theileria parasites","volume":"23","author":"Azirwan","year":"2013","journal-title":"J. Protozool. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.1128\/AAC.00022-14","article-title":"Evaluation of a fluorescence-based method for antibabesial drug screening","volume":"58","author":"Guswanto","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0125276","article-title":"Optimization of a fluorescence-based assay for large-scale drug screening against Babesia and Theileria parasites","volume":"10","author":"Rizk","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.phymed.2009.10.016","article-title":"Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats","volume":"17","author":"Lakshmi","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"24397","DOI":"10.1074\/jbc.M112.344432","article-title":"Limonoid compounds inhibit sphingomyelin biosynthesis by preventing CERT protein-dependent extraction of ceramides from the endoplasmic reticulum","volume":"287","author":"Tomishige","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1159\/000362962","article-title":"Stimulation of erythrocyte cell membrane scrambling by gedunin","volume":"33","author":"Lupescu","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"12414","DOI":"10.1073\/pnas.1508755112","article-title":"Disease-proportional proteasomal degradation of missense dystrophins","volume":"112","author":"Talsness","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00011-006-5161-8","article-title":"Antiinflammatory effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on zymosan-induced arthritis in mice","volume":"55","author":"Penido","year":"2006","journal-title":"Inflamm. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.3390\/molecules20022636","article-title":"Effect of gedunin on acute articular inflammation and hypernociception in mice","volume":"20","author":"Conte","year":"2015","journal-title":"Molecules"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.fitote.2014.09.003","article-title":"Andirolides W\u2013Y from the flower oil of andiroba (Carapa guianensis, Meliaceae)","volume":"100","author":"Sakamoto","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ninomiya, K., Miyazawa, S., Ozeki, K., Matsuo, N., Muraoka, O., Kikuchi, T., Yamada, T., Tanaka, R., and Morikawa, T. (2016). Hepatoprotective limonoids from andiroba (Carapa guianensis). Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040591"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.5650\/jos.ess18143","article-title":"Collagen synthesis-promoting effects of andiroba oil and its limonoid constituents in normal human dermal fibroblasts","volume":"67","author":"Morikawa","year":"2018","journal-title":"J. Oleo Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/3\/493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:30:22Z","timestamp":1760362222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/3\/493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,23]]},"references-count":114,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["molecules25030493"],"URL":"https:\/\/doi.org\/10.3390\/molecules25030493","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,23]]}}}