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Acetophenone-Based 3,4-Dihydropyrimidine-2(1H)-Thione as Potential Inhibitor of Tyrosinase and Ribonucleotide Reductase: Facile Synthesis, Crystal Structure, In-Vitro and In-Silico Investigations

Summary

Scientists created a new chemical compound that shows promise in fighting skin cancer, particularly melanoma. The compound is seven times more effective at blocking tyrosinase, an enzyme involved in skin pigmentation and cancer growth, compared to existing drugs. Computer simulations and laboratory tests confirmed that this compound can also interfere with DNA replication processes that cancer cells depend on, suggesting it could be developed into a new cancer treatment with fewer side effects.

Background

Melanoma and skin cancer represent significant global health concerns with high mortality rates. Tyrosinase and ribonucleotide reductase (RNR) are key enzymes involved in melanin synthesis and DNA replication, respectively. Developing inhibitors against these enzymes is an emerging strategy for cancer treatment.

Objective

To synthesize and characterize an acetophenone-based 3,4-dihydropyrimidine-2(1H)-thione compound and evaluate its potential as an inhibitor of tyrosinase and ribonucleotide reductase through in-vitro and computational studies.

Results

The compound showed 7-fold greater tyrosinase inhibition (IC50 = 1.97 μM) compared to reference drug kojic acid. Molecular docking revealed binding energies of -19.70 kJ/mol with tyrosinase, -19.68 kJ/mol with RNR, and -21.32 kJ/mol with DNA. Crystal structure analysis confirmed envelope conformation with dominant H···H interactions (59.5%) in crystal packing.

Conclusion

The acetophenone-based 3,4-dihydropyrimidine-2(1H)-thione compound demonstrates potent multi-target inhibitory potential against tyrosinase and RNR with effective DNA groove binding properties, warranting further exploration for cancer treatment development.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Experimental Research,
  • Source: PMID: 36361953, DOI: 10.3390/ijms232113164
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