Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401

Abstract

A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo₂ (OAc)₄-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC₅₀ values of 1.3-2.5 μM, and an in silico molecular docking study was also performed.

Keywords: AChE inhibitory; Cochliobolus lunatus; absolute configurations; lipopeptides; phthalide.

Figure 1

Compounds 1–6, isolated from fungal strain SCSIO41401.

Figure 2

The key HMBC, COSY, and ROESY correlations of 1–3.

Figure 3

(A) Experimental CD spectra of 1, and the calculated ECD spectra of its truncated models. (B) Experimental CD spectra of 2, and the calculated ECD spectra of its truncated models. (C) Experimental CD spectra of 3 in MeOH. (D) Induced CD (ICD) spectra from the Mo₂-complexes of 3 in DMSO.

Figure 4

Molecular docking of 1–3 with AChE (PDB code: 4EY7). The binding sites of the molecules 1 (A1), 2 (A2) and 3 (A3) with the AChE protein. The 2D interaction details of the predicted binding mode of 1 (B1), 2 (B2) and 3 (B3) with the AChE.