Thiopurines Analogues with Additional Ring: Synthesis, Spectroscopic Properties, and Anticancer Potency

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Biochemistry

Background:

• Purine scaffolds are crucial for developing diverse chemotherapeutics.
• Existing purine analogues are used to treat various diseases, including cancer, viral, parasitic, bacterial, and fungal infections.

Purpose of the Study:

• To synthesize novel guanosine analogues with a five-membered ring and a sulfur atom at the C-9 position.
• To investigate the spectral, photophysical, and biological properties of these synthesized compounds.
• To evaluate their potential as anticancer agents.

Main Methods:

• Synthesis of guanosine analogues incorporating a sulfur atom.
• Spectroscopic and photophysical characterization.
• In silico ADME (Absorption, Distribution, Metabolism, and Excretion) and PASS (Prediction of Activity Spectra for Substances) analyses.
• In vitro evaluation of cytotoxicity against human cervical carcinoma (HeLa) and mouse fibroblast (NIH/3T3) cells.

Main Results:

• The synthesized guanosine analogues exhibit absorption above 350 nm due to the thiocarbonyl chromophore and tricyclic guanine structure.
• Low fluorescence quantum yield limits their use for cellular monitoring.
• All synthesized compounds demonstrated significant anticancer activity against both HeLa and NIH/3T3 cell lines.
• In silico analyses predicted favorable ADME properties and potential biological activities.

Conclusions:

• Novel sulfur-containing guanosine analogues possess potent anticancer properties.
• These compounds are promising candidates for further development as anticancer chemotherapeutics.
• The spectral properties allow for selective excitation, although fluorescence is not suitable for cellular tracking.