Monopalmityloxy shikimic acid: enzymatic synthesis and anticoagulation activity evaluation

Area of Science:

• Biochemistry
• Pharmacology
• Organic Synthesis

Background:

• Developing novel anticoagulants is crucial for managing thrombotic disorders.
• Shikimic acid derivatives offer a potential scaffold for new therapeutic agents.

Purpose of the Study:

• To synthesize monopalmityloxy shikimic acids using enzymatic catalysis.
• To evaluate the in vivo and in vitro anticoagulation activity of the synthesized compounds.

Main Methods:

• Enzymatic synthesis of monopalmityloxy shikimic acids from shikimic acid and palmitic acid using Novozym 435.
• In vivo anticoagulation assessment using rat arteriovenous shunt models.
• In vitro coagulation tests including thrombin time, prothrombin time, and activated partial thromboplastin time.
• High-performance liquid chromatography-mass spectroscopy (HPLC-MS) for product identification and conversion rate determination.

Main Results:

• Monopalmityloxy shikimic acids were successfully synthesized with over 70% conversion rate.
• The synthesized compounds demonstrated significant anti-thrombosis activity in vivo, prolonging coagulating and bleeding times.
• In vitro studies showed prolonged coagulation times, with significant differences observed in thrombin time, prothrombin time, and activated partial thromboplastin time compared to control and aspirin groups (P < 0.05, P < 0.01).

Conclusions:

• Monopalmityloxy shikimic acids possess notable anticoagulation properties.
• The mechanism of action involves simultaneous inhibition of intrinsic and extrinsic coagulation pathways, with a stronger effect on the intrinsic pathway.
• These findings suggest potential therapeutic applications for monopalmityloxy shikimic acids in preventing and treating thrombosis.