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Structure-Based Optimization and Biological Evaluation of Pancreatic Lipase Inhibitors as Novel Potential Antiobesity Agents.

ABSTRACT: The unusual fused ?-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase. In this study, a structure-based lead optimization of vibralactone resulted in three series of 104 analogs, among which compound C1 exhibited the most potent inhibition of pancreatic lipase, with an IC50 value of 14 nM. This activity is more than 3000-fold higher than that of vibralactone. The effect of compound C1 on obesity was investigated using high-fat diet (HFD)-induced C57BL/6 J obese mice. Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity, primarily through the improvement of metabolic parameters, such as triglyceride levels.

SUBMITTER: Wei K

PROVIDER: S-EPMC4488150 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Structure-Based Optimization and Biological Evaluation of Pancreatic Lipase Inhibitors as Novel Potential Antiobesity Agents.

Wei Kun K Wang Gang-Qiang GQ Bai Xue X Niu Yan-Fen YF Chen He-Ping HP Wen Chun-Nan CN Li Zheng-Hui ZH Dong Ze-Jun ZJ Zuo Zhi-Li ZL Xiong Wen-Yong WY Liu Ji-Kai JK

Natural products and bioprospecting 20150618 3

The unusual fused β-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase. In this study, a structure-based lead optimization of vibralactone resulted in three series of 104 analogs, among which compound C1 exhibited the most potent inhibition of pancreatic lipase, with an IC50 value of 14 nM. This activity is more than 3000-fold higher than that of vibralactone. The effect of compound C1 on obesity ...[more]

PMID: 26085282

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