Design and Synthesis of Novel Antioxidant 2-Substituted-5,7,8-Trimethyl-1,4-Benzoxazine Hybrids: Effects on Young and...

Area of Science:

• Medicinal Chemistry
• Biogerontology
• Cosmetic Science

Background:

• Global aging population increases age-related disorders and cellular senescence.
• Oxidative stress is a key factor in aging and senescence.
• Antioxidants targeting senescence are crucial for anti-aging research.

Purpose of the Study:

• Synthesize novel 5,7,8-trimethyl-1,4-benzoxazine/catechol or resorcinol hybrids.
• Evaluate antioxidant capacity and intracellular reactive oxygen species (ROS) reduction in human skin fibroblasts.
• Assess the potential of these compounds in cosmetic applications for skin aging.

Main Methods:

• Synthesis of six novel benzoxazine hybrids with triazole linkers.
• Cell-free antioxidant capacity assays.
• Intracellular ROS level measurement in young and senescent human skin fibroblasts.
• Gene expression analysis of heme oxygenase-1 (HO-1) and glutathione (GSH) levels.

Main Results:

• Catechol derivatives demonstrated higher potency than resorcinol analogues.
• The most effective compounds acted as radical scavengers and ROS inhibitors.
• These derivatives induced HO-1 gene expression and enhanced GSH levels.
• One catechol derivative improved human skin fibroblast viability.

Conclusions:

• The synthesized benzoxazine hybrids, particularly catechol derivatives, exhibit significant antioxidant properties.
• These compounds effectively combat oxidative stress and support cellular redox homeostasis.
• The findings support the potential utility of these novel compounds in anti-aging cosmetic formulations.