Benzyl‐Triazole Derivatives of Hydrazinecarbothiamide Derivatives as Potent Tyrosinase Inhibitors: Synthesis, Biological Evaluation, Structure‐Activity Relationship and Docking Study. Issue 8 (20th February 2023)

• Record Type: Journal Article
• Authors: Divar, Masoumeh; Tadayyon, Somayeh; Khoshneviszadeh, Mehdi; Pirhadi, Somayeh; Attarroshan, Mahshid; Mobaraki, Kourosh; Damghani, Tahereh; Mirfazli, Sara; Edraki, Najmeh
• Is Part Of: ChemistrySelect. Volume 8:Issue 8(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-20
• Subjects: Antioxidant -- Docking -- 1, 2, 3-Triazol-benzylidenehydrazine -- Synthesis -- Tyrosinase inhibitor; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202203382
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Skin and hair pigmentation, skin cancer, and enzymatic browning of plants and fruits are caused by tyrosinase, a di‐copper oxidase. In the present work, we developed a novel series of substituted benzyl‐1, 2, 3‐triazole derivatives linked to hydrazinecarbothiamide via methoxyphenyl linker and assessed them for their tyrosinase inhibitory effects in the presence of L‐dopa as substrates. The majority of the synthesized compounds inhibited tyrosinase at sub‐micromolar concentrations. Compounds with 3, 4‐dichloro, 4‐fluoro, and 3‐chloro on the benzyl ring, respectively, exhibited exceptionally high potency against tyrosinase with IC50 values of 0.22, 0.22, and 0.24 μM in the presence of L‐dopa as substrates, which is significantly lower than that of kojic acid as the positive control with an IC50 value of 9.64 μM. Result of kinetic assay demonstrated mixed type of inhibition by 9 g. The experimental findings of the potent compounds with the target enzyme, tyrosinase, were corroborated by molecular docking studies. The results of the molecular docking analysis showed the presence of critical pi‐pi interactions between potent compounds and residues Phe264, and His263. Abstract : Novel series of benzyl‐1, 2, 3‐triazole derivatives linked to hydrazinecarbothiamide via methoxyphenyl linker were designed and synthsized as tyrsinase inhibitors. Derivatives bearing chlorine or fluorine substitute at benzyl pendant demonstrated promising tyrosinase inhitory potential in enzymatic assay. Molecular docking analysis showed critical biniding interactions with key residues of tyrosinase acive site.