Navigating Dipeptide by a Nucleoside Moiety: A Promising Way for Enhancing Antioxidative Effect against...

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Biochemistry

Background:

• Developing effective antioxidants to prevent radical-induced DNA oxidation remains a significant challenge.
• The Ugi four-component reaction (Ugi 4CR) has been identified as an efficient method for synthesizing antioxidative dipeptides.

Purpose of the Study:

• To design and synthesize novel nucleoside-appended dipeptides with enhanced antioxidant properties.
• To investigate the efficacy of these novel compounds in protecting DNA against peroxyl-radical-induced oxidation.

Main Methods:

• Utilizing the Ugi four-component reaction (Ugi 4CR) to create dipeptides.
• Conjugating these dipeptides to a nucleoside moiety via a succinate linker, targeting the 5'-OH group.
• Evaluating the antioxidative effects of the synthesized compounds on DNA protection against peroxyl radicals.

Main Results:

• Nucleoside-appended dipeptides demonstrated a 2-3 fold enhancement in antioxidative effects compared to parent dipeptides.
• The enhanced activity is attributed to improved DNA intercalation by the nucleoside moiety and radical scavenging by its functional groups.
• The Ugi 4CR products, when appended with nucleosides, showed superior protection against DNA oxidation.

Conclusions:

• Appending nucleoside moieties to Ugi 4CR-derived dipeptides is a versatile strategy for creating potent DNA-protective antioxidants.
• The enhanced efficacy stems from the nucleoside's ability to intercalate into DNA and participate in radical scavenging.
• This approach offers a promising avenue for developing novel antioxidants against oxidative DNA damage.