Synthesis of benzamide derivatives and evaluation of their in vitro and in silico tyrosinase  inhibitory activities

Tran Hoai Tu; Nguyen Trung Nhan; Dang Hoang Phu

doi:10.15625/2525-2518/18302

Author affiliations

Authors

Tran Hoai Tu Faculty of Chemistry, University of Science, 227 Nguyen Van Cu street, District 5, Ho Chi Minh City 72711, Viet Nam
Nguyen Trung Nhan Faculty of Chemistry, University of Science, 227 Nguyen Van Cu street, District 5, Ho Chi Minh City 72711, Viet Nam
Dang Hoang Phu 2Vietnam National University Ho Chi Minh City, Linh Trung Ward, Thu Duc City, Ho Chi Minh City, Viet Nam https://orcid.org/0000-0002-4989-9315

DOI:

https://doi.org/10.15625/2525-2518/18302

Keywords:

benzamide derivatives, tyrosinase inhibitory activity, docking studies

Abstract

In this research, six benzamide derivatives were traditionally synthesized using hydrazine, carbazide, and hydroxylamine derivatives through the pre- or in situ activation of the carboxylic acid functionality. Their chemical structures were identified as N′-phenylbenzohydrazide, N′-(2,4-dinitrophenyl)benzohydrazide, N′-(benzoyloxy)benzamide, N-dibenzoylurea, 2-amino-5-(4-phenyl)-1,3,4-thiadiazole, and benzohydrazide based on the interpretation of NMR spectroscopic data. Among these products, N′-phenylbenzohydrazide and N-(benzoyloxy)benzamide showed potent tyrosinase inhibitory activity with the IC₅₀ values of 10.5 and 2.5 μM, respectively, stronger than that of kojic acid (44.6 μM). Docking studies between oxy-tyrosinase and the two active compounds have been carried out to analyze their binding interactions. Both two active compounds showed negative binding free energy values (S values) and some more interactions than the positive control (kojic acid). This discovery provided evidence for the potent tyrosinase inhibitory activity of these two compounds, making them promising candidates for the development of anti-tyrosinase agents in medicine and cosmetics.

Downloads

Download data is not yet available.

References

Chawla S., Delong M. A., Visscher M. O., Wickett R. R., Manga P., Boissy R. E. - Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation derivatives, Br. J. Dermatol. 159 (2008) 1267-1274. doi.org/10.1111/j.1365-2133.2008.08864.x.

Rodriguez-Lopez J. N., Tudela J., Varon R., Garcia-Carmona F., Garcia-Canovas F. - Analysis of a kinetic model for melanin biosynthesis pathway, J. Biol. Chem. 267 (1992) 3801-3810. doi.org/10.1016/S0021-9258(19)50597-X.

Decker H., Tuczek F. - Tyrosinase/catecholoxidase activity of hemocyanins: structural basis and molecular mechanism, Trends. Biochem. Sci. 25 (2000) 392-397. doi.org/10.1016/s0968-0004(00)01602-9.

Pillaiyar T., Manickam M., Namasivayam V. - Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors, J. Enzyme Inhib. Med. Chem. 32 (2017) 403-425. doi.org/10.1080/14756366.2016.1256882.

Kushwaha N., Saini R. K., Kushwaha S. K. - Synthesis of some amide derivatives and their biological activity, Int. J. ChemTech. Res. 3 (2011) 203-209.

Khan S. B., Khan M. T. H., Jang E. S., Akhtar K., Seo J., Han H. - Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships, J. Enzyme Inhib. Med. Chem. 25 (2010) 812-817. doi.org/10.3109/14756366.2010.482529.

Lee S., Ullah S., Park C., Lee H. W., Kang D., Yang J., Akter J., Park Y., Chun P., Moon H. R. - Inhibitory effects of N-(acryloyl)benzamide derivatives on tyrosinase and melanogenesis, Bioorg. Med. Chem. 27 (2019) 3929-3937. doi.org/10.1016/j.bmc.2019.07.034.

McMurry J. - Organic Chemistry, 9th ed., Cornell University, United States (2015).

Isabella R., Giorgio F. - Different Schiff basesStructure, importance and classification, Molecules. 27 (2022) 787-795. doi.org/10.3390/molecules27030787.

Christopher A. R., Patrick A. R. - Tyrosinase: The four oxidation states of the active site and their relevance to enzymatic activation, oxidation and inactivation, Bioorg. Med. Chem. 22 (2014) 2388-2395. doi.org/10.1016/j.bmc.2014.02.048.

Matoba Y., Kumagai T., Yamamoto A., Yoshitsu H., Sugiyama M. - Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis, J. Biol. Chem. 281 (2006) 8981-8990. doi.org/10.1074/jbc.M509785200.

Choi J., Lee Y. M., Jee J. G. - Thiopurine drugs repositioned as tyrosinase inhibitors, Int. J. Mol. Sci. 19 (2018) 77-92. doi.org/10.3390/ijms19010077.

Chemical Computing Group. - Molecular operating environment (MOE) 2016, Chemical Computing Group, Montreal, QC, Canada, 2016.

Dassault Systèmes BIOVIA. - BIOVIA Discovery Studio Visualizer, Dassault Systèmes BIOVIA, San Diego, CA, USA, 2016.