Squarate-based carbocyclic nucleosides: Syntheses, computational analyses and anticancer/antiviral evaluation

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Nucleoside Analog Development

Background:

• Squaric acid derivatives are recognized as versatile synthons in medicinal chemistry.
• They serve as effective bioisosteric replacements for various functional groups in drug design.
• However, their potential as nucleobase analogs in nucleosides remains unexplored.

Purpose of the Study:

• To investigate the novel application of squaric acid derivatives as nucleobase substitutes in nucleosides.
• To synthesize novel squaric acid-based nucleoside analogs.
• To evaluate the preliminary biological activity of these synthesized compounds.

Main Methods:

• Synthesis of three novel squaric acid derivatives incorporating a cyclopentene moiety.
• Structural analysis using computational methods.
• Preliminary screening for antitumor and antiviral properties.

Main Results:

• Successful synthesis of 3-amino-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione, 3-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-4-methoxycyclobut-3-ene-1,2-dione, and 3-hydroxy-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione sodium salt.
• Computational analysis provided insights into the structures of the synthesized compounds.
• Preliminary screening indicated potential antitumor and antiviral activities.

Conclusions:

• Squaric acid derivatives show promise as a new class of nucleobase analogs.
• The synthesized compounds warrant further investigation for their therapeutic potential.
• This study opens new avenues for drug discovery utilizing squaric acid chemistry.