A Series of Benzylidenes Linked to Hydrazine-1-carbothioamide as Tyrosinase Inhibitors: Synthesis, Biological Evaluation and Structure-Activity Relationship

被引：28

作者：

Hosseinpoor, Hona ^{[1
,2
]}

Iraji, Aida ^{[1
,3
]}

Edraki, Najmeh ^{[1
]}

Pirhadi, Somayeh ^{[1
]}

Attarroshan, Mahshid ^{[1
]}

Khoshneviszadeh, Mahsima ^{[1
]}

Khoshneviszadeh, Mehdi ^{[1
,2
]}

机构：

[1] Shiraz Univ Med Sci, Med & Nat Prod Chem Res Ctr, Shiraz 71348, Iran

[2] Shiraz Univ Med Sci, Fac Pharm, Dept Med Chem, Shiraz 71345, Iran

[3] Shiraz Univ Med Sci, Cent Res Lab, Shiraz 71468, Iran

来源：

CHEMISTRY & BIODIVERSITY | 2020年 / 17卷 / 08期

关键词：

tyrosinase inhibitor; organic synthesis; antioxidant assay; pharmacophore modeling; molecular docking; ANTIOXIDANT ACTIVITY; ANTIRADICAL ACTIVITIES; DERIVATIVES; ACETYLCHOLINESTERASE; BROMOPHENOLS;

D O I：

10.1002/cbdv.202000285

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tyrosinase is a type 3 copper enzyme responsible for skin pigmentation disorders, skin cancer, and enzymatic browning of vegetables and fruits. In the present article, 12 small molecules of 2-benzylidenehydrazine-1-carbothioamide were designed, synthesized and evaluated for their anti-tyrosinase activities followed by molecular docking and pharmacophore-based screening. Among synthesized thiosemicarbazone derivatives, one compound, (2E)-2-[(4-nitrophenyl)methylidene]hydrazine-1-carbothioamide, is the strongest inhibitor of mushroom tyrosinase with IC(50)of 0.05 mu M which demonstrated a 128-fold increase in potency compared to the positive control. Kinetic studies also revealed mix type inhibition by this compound. Docking studies confirmed the complete fitting of the synthesized compounds into the tyrosinase active site. The results underline the potential of 2-benzylidenehydrazine-1-carbothioamides as potent pharmacophore to extend the tyrosinase inhibition in drug discovery.

引用

页数：12

共 40 条

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