Thiosemicarbazones as inhibitors of tyrosinase enzyme. Issue 15 (1st August 2017)

• Record Type: Journal Article
• Authors: Soares, Mariana A.; Almeida, Mariana A.; Marins-Goulart, Carla; Chaves, Otávio A.; Echevarria, Aurea; de Oliveira, Márcia C.C.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 15(2017)
• Page Start: 3546
• Page End: 3550
• Publication Date: 2017-08-01
• Subjects: Melanin -- Phenol oxidase -- Melanome -- Thiosemicarbazones -- Molecular docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.05.057
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. ThiosemicarbazonesThio-1, Thio-2, Thio-3 andThio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44 mM, respectively) thanThio-5, Thio-6, Thio-7 andThio-8 . For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu 2+ ions. Inside the active protein pocket, Thio-2 – the best studied inhibitor – is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force.Thio-2, containing a substituent on the aromatic ring similar to the substratel -DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver–Burk plot. The same results were observed in the UV–Vis curves.