CAPE derivatives: Multifaceted agents for chronic wound healing

Area of Science:

• Biochemistry
• Dermatology
• Medicinal Chemistry

Background:

• Chronic wounds present a significant clinical challenge, necessitating the development of advanced therapeutic agents.
• Caffeic acid phenethyl ester (CAPE) shows potential for skin regeneration but suffers from poor stability.
• Chemical modification of CAPE can improve its pharmacokinetic properties and therapeutic efficacy.

Purpose of the Study:

• To design, synthesize, and evaluate novel CAPE hybrids with enhanced stability and skin regenerative properties.
• To investigate the effects of these derivatives on cell viability, proliferation, and wound healing.
• To assess antimicrobial, antioxidant, and stability characteristics of the synthesized compounds.

Main Methods:

• Synthesis of two novel series of CAPE hybrids (ester and amide linkages with quinolines/isoquinolines).
• In vitro assays evaluating cytotoxicity, cell proliferation (HGFs and HaCaT cells), and wound healing.
• Assessment of antimicrobial, antioxidant, chemical, and thermal stability.
• In silico prediction of skin penetration.

Main Results:

• Synthesized CAPE derivatives (1a-f and 2a-f) were non-cytotoxic and some stimulated cell proliferation.
• Compounds 1a and 1d demonstrated significant wound healing potential in vitro.
• These derivatives exhibited antimicrobial and antioxidant activities, along with good chemical and thermal stability.
• In silico analysis suggested favorable skin penetration capabilities.

Conclusions:

• Novel CAPE derivatives, particularly 1a and 1d, show significant therapeutic potential for chronic wound healing.
• These compounds offer a multitargeted approach by stimulating proliferation, controlling bacteria, and managing oxidative stress.
• Improved stability and potential for enhanced skin penetration make these derivatives promising candidates for pharmaceutical development.