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 |
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