{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:08:12Z","timestamp":1783728492876,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Foundation of the Third Institute of Oceanography, Ministry of Natural Resources","award":["2018013"],"award-info":[{"award-number":["2018013"]}]},{"name":"Xiamen Marine Economic Innovation and Development Demonstration Project","award":["16CZP012SF04"],"award-info":[{"award-number":["16CZP012SF04"]}]},{"name":"Beihai Marine Economic Innovation and Development Demonstration Project","award":["Bhsfs010"],"award-info":[{"award-number":["Bhsfs010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>In recent years, a large number of pharmacologically active compounds containing a butenolide functional group have been isolated from secondary metabolites of marine microorganisms. Butyrolactone I was found to be produced by Aspergillus terreus isolated from several marine-derived samples. The hypoglycemic activity of butyrolactone I has aroused our great interest. In this study, we synthesized six racemic butenolide derivatives (namely BL-1\u2013BL-6) by modifying the C-4 side chain of butyrolactone I. Among them, BL-3 and BL-5 improved the insulin resistance of HepG2 cells and did not affect the proliferation of RIN-m5f cell line, which indicated the efficacy and safety of BL-3 and BL-5. Furthermore, BL-3, BL-4, BL-5, and BL-6 displayed a significant protein tyrosine phosphatase 1B (PTP1B) inhibitory effect, while the enantiomers of BL-3 displayed different 50% percentage inhibition concentration (IC50) values against PTP1B. The results of molecular docking simulation of the BLs and PTP1B explained the differences of biological consequences observed between the enantiomers of BL-3, which supported BLs as PTP1B inhibitors, and also indicated that the chirality of C-4 might influence the inhibitory effect of the BLs. Our findings provide a novel strategy for the development of butyrolactone derivatives as potential PTP1B inhibitors for the treatment of type 2 diabetes mellitus.<\/jats:p>","DOI":"10.3390\/md18110526","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T02:34:54Z","timestamp":1603679694000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and Biological Evaluation of Analogues of Butyrolactone I as PTP1B Inhibitors"],"prefix":"10.3390","volume":"18","author":[{"given":"Bihong","family":"Hong","sequence":"first","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-5767","authenticated-orcid":false,"given":"Jianlin","family":"He","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochun","family":"Fan","sequence":"additional","affiliation":[{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Tang","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Le","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Bai","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Niu","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meitian","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"ref_1","unstructured":"Kumar, V., Fausto, N., Abbas, A.K., Cotran, R.S., and Robbins, S.L. 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