1. Pancreatic Lipase Inhibitory Cyclohexapeptides from the Marine Sponge-Derived Fungus Aspergillus sp. 151304
- Author
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Jing-Tang Liu, Guang-Bo Ge, Xiao-Qing Guan, Hua Han, Rong-Jing He, Fan Yang, Wei-Zhuo Tang, Qing Hu, and Hou-Wen Lin
- Subjects
Pharmacology ,Aspergillus ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Pharmaceutical Science ,Fungus ,Inhibition kinetics ,Inhibitory postsynaptic potential ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Catalysis ,010404 medicinal & biomolecular chemistry ,Sponge ,Complementary and alternative medicine ,Drug Discovery ,Ic50 values ,biology.protein ,Molecular Medicine ,Pancreatic lipase - Abstract
Three new cyclohexapeptides, petrosamides A-C (1-3), were isolated from the sponge-derived fungus Aspergillus sp. 151304. Their structures were elucidated by detailed 1D and 2D spectroscopic analyses, and the absolute configurations of the amino acid residues were determined by the advanced Marfey's method. These peptides displayed significant and dose-dependent pancreatic lipase (PL) inhibitory activities, with IC50 values of 7.6 ± 1.5, 1.8 ± 0.3, and 0.5 ± 0.1 μM, respectively. Further inhibition kinetics analyses showed that compound 3 inhibited PL in a noncompetitive manner, while molecular dynamics simulation revealed that it could bind to PL at the entrance of the catalytic pocket.
- Published
- 2020