The unusual fused b-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 optimiza...The unusual fused b-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.展开更多
Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elu...Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.展开更多
The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, an...The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.展开更多
基金The authors are grateful to the National Natural Science Foundation of China(81102348,U1132607,81373289).
文摘The unusual fused b-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.
基金supported by the National Natural Science Foundation of China(Nos.81803397 and 81522050)the Science and Technology program of Qinghai Province(No.2018-ZJ-739)+1 种基金the Drug Innovation Major Project(Nos.2018ZX09711001-001-001,2018ZX09711001-001-003,and 2018ZX09711001-001-008)the Special Research Fund for Central Universities,Peking Union Medical College(No.3332018088)
文摘Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.
基金supported by the Graduate Students Scientific Research Innovation Projects of Jiangsu Province(No:CXZZ11-0804)
文摘The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, 1H NMR and 13 C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
