Qi_2018_Org.Biomol.Chem_16_9046

Reference

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract :

Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.

PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

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Citations formats

Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J, Li D, Wang J, Zhu H, Hu Z, Zhou Y, Zhang Y (2018)
New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus
Org Biomol Chem 16 :9046

Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J, Li D, Wang J, Zhu H, Hu Z, Zhou Y, Zhang Y (2018)
Org Biomol Chem 16 :9046