Revisiting Polyarenes and Related Molecules: An Update of Synthetic Approaches and Structure-Activity-Mechanistic...

Area of Science:

• Environmental Science
• Toxicology
• Medicinal Chemistry

Background:

• Environmental pollutants, particularly polyarenes, are significant contributors to human cancer.
• Understanding the generation and biological interactions of these carcinogens is key to developing effective therapies.

Purpose of the Study:

• To review the syntheses, structural activities, and biological studies of polyarenes, including polycyclic aromatic hydrocarbons (PAHs), polycyclic azaarenes (PAAs), and their thia-analogs (PASH).
• To summarize the mechanisms of mutagenicity and tumorigenicity involving metabolic activation and DNA adduct formation.
• To suggest therapeutic strategies for preventing and treating cancer caused by these environmental pollutants.

Main Methods:

• Literature review focusing on syntheses and structural activities of polyarenes.
• Analysis of mechanistic and biological studies on mutagenicity and tumorigenicity.
• Examination of metabolic pathways, including diol epoxide formation and DNA adducts.
• Review of potential therapeutic interventions targeting metabolic activation.

Main Results:

• Polyarenes undergo metabolic activation to form diol epoxides, leading to DNA adducts and subsequent mutagenicity and tumorigenicity.
• Inhibiting oxidative reactions and specific metabolic activation pathways presents a potential therapeutic strategy.
• Understanding molecular mechanisms and activation pathways is vital for clinical and translational medicine.

Conclusions:

• Targeting the metabolic activation of polyarenes offers a promising approach for cancer prevention and treatment.
• A multidisciplinary approach combining molecular understanding with clinical and translational medicine is necessary.
• Further research into the biological interactions and therapeutic inhibition of polyarene carcinogenicity is warranted.