Isolation, Structural Characterization and Antidiabetic Activity of New Diketopiperazine Alkaloids from Mangrove Endophytic Fungus Aspergillus sp. 16-5c

Abstract

Six new DIKETOPIPERAZINE alkaloids aspergiamides A–F (1–6), together with ten known alkaloids (7–16), were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5c. The structures of the new compounds were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of aspergiamides A-F were established based on the experimental and calculated ECD data. All the compounds were evaluated for the antidiabetic activity against α-glucosidase and PTP1B enzyme. The bioassay results disclosed compounds 1 and 9 exhibited significant α-glucosidase inhibitory with IC50 values of 18.2 and 7.6 μM, respectively; compounds 3, 10, 11, and 15 exhibited moderate α-glucosidase inhibition with IC50 values ranging from 40.7 to 83.9 μM; while no compounds showed obvious PTP1B enzyme inhibition activity.

Unambiguous Stereochemical Assignment of Cyclo(Phe-Pro), Cyclo(Leu-Pro), and Cyclo(Val-Pro) by Electronic Circular Dichroic Spectroscopy

“…The theoretical approach is important, especially for DKPs that are not readily obtained by synthesis. In fact, theoretical ECD has recently become an important approach for stereochemical analysis of structurally complex DKPs from natural sources [ 21 , 22 ]. Another possible alternative approach is the use of vibrational CD (VCD), which has become a powerful method for determining absolute configuration of natural products [ 23 ].…”

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

“…Antihyperglycaemic activity of DKPs is well-documented in the literature [310,311]. Proline-based DKP alkaloids, from marine fungi, can provide a new platform for the discovery of a drug [312]. Cyclo(His-Pro) decreases the level of blood glucose [176].…”

“…DKP alkaloids are important secondary metabolites of microbes. Indole DKP alkaloids are the condensation products of tryptophan with a second amino acid-like L-proline [105,312,331].…”

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

“…The genus Aspergillus is omnipresent among almost all ecosystems even the circumpolar maritime regions [ 1 ]. Previous investigations on Aspergillus genus indicated that it was rich in bioactive secondary metabolites with multifarious and intricate structures such as sesquiterpenoids [ 2 , 3 ], meroterpenoids [ 4 , 5 ], alkaloids [ 6 , 7 ], and polyketides [ 8 ]. Some of the natural products isolated from Aspergillus genus possessed cytotoxic, antimicrobial, acetylcholinesterase inhibitory, and PTP1B enzyme inhibitory activities [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], which have attracted great interest of natural chemists.…”

“…Previous investigations on Aspergillus genus indicated that it was rich in bioactive secondary metabolites with multifarious and intricate structures such as sesquiterpenoids [ 2 , 3 ], meroterpenoids [ 4 , 5 ], alkaloids [ 6 , 7 ], and polyketides [ 8 ]. Some of the natural products isolated from Aspergillus genus possessed cytotoxic, antimicrobial, acetylcholinesterase inhibitory, and PTP1B enzyme inhibitory activities [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], which have attracted great interest of natural chemists. Bisabolanes, a class of sesquiterpenoids possessing diverse skeletons including aromatic monomers and their home/hetero-dimers, are mainly distributed in plant kingdom, marine-derived animals, and fungi [ 9 ].…”