Work

Abastatins A–C: Cathepsin D‐Inhibitory Depsipeptides From a Marine Okeania sp. Cyanobacterium

Year: 2026

Type: article

Abstract: ABSTRACT Statine [(3 S ,4 S )‐4‐amino‐3‐hydroxy‐6‐methylheptanoic acid (Sta)] is a γ‐amino acid produced by several microorganisms, including actinomycetes and cyanobacteria. Sta‐containing natural products are known to inhibit cathepsin D, a promising therapeutic target for cancer and neurodegenerative diseases. In this study, three new Sta‐containing natural products, abastatins A–C, were isolated from a marine Okeania sp. cyanobacterium collected in Japan. Their structures were unambiguously elucidated by spectroscopic analyses combined with derivatization and degradation reactions. To date, Sta‐containing natural products have been discovered mainly from marine cyanobacteria; among them, abastatins A–C exhibit the most potent cathepsin D inhibitory activities reported thus far with IC 50 values in the picomolar range. In addition, we propose plausible docking poses for abastatins A–C bound to cathepsin D and describe a new structure‐activity relationship that can enhance inhibitory potency against this enzyme.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.71051

Authors: Yuma Yamaji, Nao Tanaka, Arihiro Iwasaki

Institution: Chuo University

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Naito Foundation, Kato Memorial Bioscience Foundation, Japan Society for the Promotion of Science