Development of carbazole-bearing pyridopyrimidine-substituted urea/thiourea as polyphenol oxidase inhibitors: synthesis, biochemistry, and theoretical studies

Abstract

Polyphenol oxidase (Tyrosinase, PPO) has received considerable attention, since it is the key enzyme in melanin biosynthesis. In this study, we investigated prepared novel carbazole-containing pyridopyrimidine-substituted with urea and thiourea derivatives and their PPO activities on the diphenolase activity of banana tyrosinase. The structures of the compounds synthesized were confirmed by 1 H NMR, 13 C NMR, FTIR and elemental analysis. PPO enzyme was purified from banana on an affinity gel comprised of Sepharose 4B-L-tyrosine-p-amino benzoic acid. For evaluating the enzyme activity, the synthesised compounds were subjected to tyrosinase inhibition assay using catechol as substrate. While some of the compounds (6, 7, 8f, 8h, 8i, 8j) showed enzyme inhibitor effect, some of them (8a, 8b, 8c, 8d, 8e, 8g, 8k) activated the PPO enzyme activity. Gaussian software was used for the molecular calculations to explain the results for the prepared compounds.

Keywords:

• Carbazole
• pyridopyrimidine
• urea
• thiourea
• polyphenol oxidase
• theoretical calculations

Acknowledgements

The authors are thankful to Dr Yusuf ATALAY for quantum chemical calculation using Gaussian Software.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was financially supported by the Research Fund provided by Sakarya University. Project Number: 2016–02-04–018, and was also supported by Balikesir University Research Project [2016/142].