Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia dactylomela with significant in vitro anti-neuroinflammatory activity

• Published in: Bioorganic & medicinal chemistry letters 2014-01, Vol.24 (1), p.344-348
• Main Authors: Jiménez-Romero, Carlos, Mayer, Alejandro M S, Rodríguez, Abimael D
• Format: Article
• Language: English
• Subjects: Absolute configuration; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aplysia; Aplysia - chemistry; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Dose-Response Relationship, Drug; Escherichia coli - chemistry; Escherichia coli - metabolism; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Microglia - drug effects; Microglia - metabolism; Models, Molecular; Molecular Conformation; Rats; Stereoisomerism; Structure-Activity Relationship; Superoxides - antagonists & inhibitors; Superoxides - metabolism; Thromboxane B2 - antagonists & inhibitors; Thromboxane B2 - biosynthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.11.008

A new regular diterpene possessing an unusual 1,6-anti-3-methylcyclohex-2-en-1-ol ring system, dactyloditerpenol acetate (1), has been extracted from the tropical sea hare Aplysia dactylomela and its stereostructure elucidated by spectroscopic methods. The absolute configuration of 1 was determined as 1S, 6S, 7R, 10S, and 11R by application of Kishi's method for the assignment of absolute configuration of alcohols. The new diterpene potently inhibited in vitro thromboxane B2 (TXB2) (IC50 0.4μM) and superoxide anion (O2(-)) (IC50 1μM) generation from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity.