Biotransformations of anthranilic acid and phthalimide to potent antihyperlipidemic alkaloids by the marine-derived fungus Scedosporium apiospermum F41-1.

Abstract

A new diphenylamine derivative, scediphenylamine A (1), together with six phthalimide derivatives (2-7) and ten other known compounds (8-17) were obtained from the marine-derived fungus Scedosporium apiospermum F41-1 fed with synthetically prepared anthranilic acid and phthalimide. The structure and absolute configuration of the new compound were determined by HRMS, NMR, and X-ray crystallography. Evaluation of their lipid-lowering effect in 3T3-L1 adipocytes showed that scediphenylamine A (1), N-phthaloyl-tryptophan-methyl ester (4), 5-(1,3-dioxoisoindolin-2-yl) pentanamide (5), perlolyrine (10) and flazine (11) significantly reduced triglyceride level in 3T3-L1 cells by inhibiting adipogenic differentiation and synthesis with the EC50 values of 4.39, 2.79, 3.76, 0.09, and 4.52 μM, respectively. Among them, perlolyrine (10) showed the most potent activity, making it a candidate for further development as a potential agent to treat hyperlipidemia.

• Authors: Pei-Nan Chen, Meng-Jiao Hao, Hou-Jin Li, Jun Xu, Taifo Mahmud, Wen-Jian Lan
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 116 Pg. 105375 (11 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 34563999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Alkaloids
• Hypolipidemic Agents
• Phthalimides
• ortho-Aminobenzoates
• anthranilic acid
• phthalimide

Topics

• 3T3-L1 Cells
• Alkaloids (chemistry)
• Animals
• Biotransformation
• Hypolipidemic Agents (chemistry)
• Mice
• Molecular Structure
• Phthalimides (chemical synthesis, chemistry)
• Scedosporium (chemistry)
• ortho-Aminobenzoates (chemical synthesis, chemistry)