Thiazol-4(5H)-one analogs as potent tyrosinase inhibitors: Synthesis, tyrosinase inhibition, antimelanogenic effect, antioxidant activity, and in silico docking simulation

被引：11

作者：

Park, Yu Jung ^{[1
,2
]}

Jung, Hee Jin ^{[1
,2
]}

Kim, Hye Jin ^{[1
,2
]}

Park, Hye Soo ^{[1
,2
]}

Lee, Jieun ^{[1
,2
]}

Yoon, Dahye ^{[1
,2
]}

Kang, Min Kyung ^{[1
,2
]}

Kim, Ga Young ^{[1
,2
]}

Ullah, Sultan ^{[3
]}

Kang, Dongwan ^{[4
]}

Park, Yujin ^{[4
]}

Chun, Pusoon ^{[5
,6
]}

Chung, Hae Young ^{[1
,7
]}

Moon, Hyung Ryong ^{[1
,2
,8
,9
]}

机构：

[1] Pusan Natl Univ, Coll Pharm, Dept Mfg Pharm, Busan 46241, South Korea

[2] Pusan Natl Univ, Res Inst Drug Dev, Busan 46241, South Korea

[3] Herbert Wertheim UF Scripps Inst Biomed Innovat &, Dept Mol Med, Jupiter, FL 33458 USA

[4] Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Dept Med Chem, Daegu 41061, South Korea

[5] Inje Univ, Coll Pharm, Gimhae 50834, South Korea

[6] Inje Univ, Inje Inst Pharmaceut Sci & Res, Gimhae 50834, South Korea

[7] Pusan Natl Univ, Coll Pharm, Dept Pharm, Busan 46241, South Korea

[8] Pusan Natl Univ, Coll Pharm, Dept Mfg Pharm, Lab Med Chem, Busan 46241, South Korea

[9] Pusan Natl Univ, Res Inst Drug Dev, Busan 46241, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2024年 / 98卷

关键词：

Mushroom tyrosinase; PUSC; Tyrosinase; Antioxidant; Melanin; Docking; Thiazol-4(5H)-one scaffold; MELANIN BIOSYNTHESIS; ACID; MELANOGENESIS; INSIGHTS; VITRO;

D O I：

10.1016/j.bmc.2023.117578

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：

As the beta-phenyl-alpha,beta-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC50 value of 0.4 +/- 0.01 mu M, which indicates its 26-fold greater potency than kojic acid. Kinetic studies using Lineweaver-Burk plots revealed that 9 and 11 are competitive and mixed-type inhibitors, respectively; these kinetic results were supported by docking simulations. According to the B16F10 cell-based experiments, 9 and 11 inhibited melanogenesis more effectively than kojic acid due to their potent cellular tyrosinase inhibitory activity. In addition, analogs 9 and 11 exhibited moderate-to-strong antioxidant capacity, scavenging ABTS+, DPPH, and ROS radicals. In particular, analog 12 with a catechol moiety exhibited very strong ROS-scavenging activity, similar to Trolox. These results suggest that analogs 9 and 11, which exhibit potent tyrosinase inhibitory activity in mushroom and mammalian cells and anti-melanogenic effects in B16F10 cells, are promising antibrowning agents for crops and skin lightening agents for hyperpigmentation-related diseases.

引用

页数：15

共 38 条

[1] 1,2,3-Triazole-based kojic acid analogs as potent tyrosinase inhibitors: Design, synthesis and biological evaluation [J].