Bisaspochalasins D and E: Two Heterocycle-Fused Cytochalasan Homodimers from an Endophytic Aspergillus flavipes

Abstract

Two heterocycle-fused cytochalasan homodimers, bisaspochalasins D (1) and E (2), were isolated from an endophytic Aspergillus f lavipes. Their chemical structures were elucidated using a combination of HRESIMS, NMR, theoretical calculations, and crystallographic techniques. Bisaspochalasin D (1) is dimerized by the first reported naturally occurring triple heterobridged 3,8-dioxa-6-azabicyclo[3.2.1]octane framework, while bisaspochalasin E (2) employs a pyrrole ring as the linking moiety. Possible dimerization mechanisms of bisaspochalasins D and E were proposed. The bioassay screening revealed that bisaspochalasin D showed cytotoxic activities against five cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) with IC 50 values ranging from 4.45 to 22.99 μM. Additionally, bisaspochalasin D exhibited neurotrophic activities in a PC12 cell-based assay. At a concentration of 10 μM, bisaspochalasin D can promote neurite growth by inducing a differentiation rate of 12.52% for PC12 cells.

Talachalasins A—C, Undescribed Cytochalasans with a 16β‐Methyl or 2‐Oxabicyclo[3.3.1]nonan‐3‐one unit from the Deep‐Sea‐Derived Fungus Talaromyces muroii sp. SCSIO 40439

“…[ 1‐3 ] To date, more than 500 CYTs analogues have been reported. [ 1,3 ] CYTs display a variety of biological activities such as antitumor, phytotoxins, virulence factors, antimicrobials, and cytotoxins, [ 1‐3 ] and have been widely discovered from fungi, including Aspergillus , [ 4‐5 ] Arthrinium, [ 6 ] Phomopsis , [ 7 ] Chaetomium , [ 8 ] Phoma multirostrata , [ 9 ] Parastagonospora nodorum , [ 10 ] Xylaria , [ 11 ] and Spicaria . [ 12 ] Biogenetically, CYTs originate from hybrid pathways of the polyketide synthase (PKS)‐nonribosomal peptide synthetase (NRPS), and undergo intramolecular Diels‐Alder (IMDA) cyclization to construct the tricyclic core scaffold.…”

Bioactive Alkaloids as Secondary Metabolites from Plant Endophytic Aspergillus Genus

“…Compound 21 showed cytotoxic activity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells with IC 50 values in the range of 4.45 to 22.99 µM. Compound 21 also displayed neurite-outgrowth activity for PC12 cells with a differentiation rate of 12.52% at 10 µM [28].…”

“…Compound 21 showed cytotoxic activity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells with IC50 values in the range of 4.45 to 22.99 μM. Compound 21 also displayed neurite-outgrowth activity for PC12 cells with a differentiation rate of 12.52% at 10 μM [28]. The endophytic fungus Aspergillus sp., associated with the Pinellia ternata tubers, produced six new seco-cytochalasins A-F (5-10), and three known cytochalasins; cytochalasin Z17 (11), cytochalasin E (12), and rosellichalasin (13).…”

Phomopsischalins A–C, polycyclic-fused cytochalasins from the endophytic fungus Phomopsis sp. shj2 and their abilities to induce lysosomal function

“…3 Identifying natural products that regulate lysosomal function is of remarkable medical interest. Cytochalasins are a large family of fungal polyketide synthase-non ribosomal peptide synthetase (PKS-NRPS) hybrid metabolites with a plethora of biological activities, including antimicrobial, 4,5 cytotoxic, [6][7][8] cancer immunotherapeutic, 9 immunoregulatory, 10 cytoskeleton inhibitory, [11][12][13] and neurotrophic activities, 14 and have aroused considerable interest. In recent years, more than 500 cytochalasins with diverse architectures have been identified, many of which have been synthesized by organic chemists in an elegant manner.…”