Halogenated aromatic thiosemicarbazones as potent inhibitors of tyrosinase and melanogenesis

Hałdys, Katarzyna; Goldeman, Waldemar; Jewgiński, Michał; Wolińska, Ewa; Anger‐Góra, Natalia; Rossowska, Joanna; Latajka, Rafał

doi:10.1016/j.bioorg.2019.103419

Cited by 25 publications

(30 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melanogenesis is a multistep process resulting in the formation of melanin pigments which are responsible for skin, hair, and eye color. [1,2] Under physiological conditions, melanin plays an important role in protecting the skin against the damaging effects of UV radiation, although its over-production can cause hyper-pigmentary disorders such as melasma, freckles, postinflammatory melanoderma, pigmented acne scars and liver spots. [3] Furthermore, the biosynthetic pathway that leads to the production of neuromelanin seems to be linked to Parkinson's disease.…”

Section: Introductionmentioning

confidence: 99%

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

et al. 2020

View full text Add to dashboard Cite

Tyrosinase is a type‐3 copper protein involved in the biosynthesis of melanin pigments; therefore, the inhibition of its enzymatic activity represents a promising strategy for the treatment of hyperpigmentation‐related disorders. To address this point, we previously designed a class of 4‐(4‐fluorobenzyl)piperazin‐1‐yl‐based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than the positive control kojic acid. Herein, we report the synthesis of further series of 4‐(4‐fluorobenzyl)piperazin‐1‐yl analogues bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The newly synthesized compounds were assayed in vitro and proved to be potent inhibitors in the low‐micromolar range. The active 2‐thienyl and 2‐furyl derivatives were selected for further modification to allow their binding mode to be analyzed by docking studies and to give satisfactory safety profiles.

show abstract

Section: Introductionmentioning

confidence: 99%

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

et al. 2020

View full text Add to dashboard Cite

show abstract

“… Ref. Inhibitor IC50 Type [ 65 ] In1 (jineol) 39.46 ± 0.01 μM L-Tyrosine Noncompetitive 50.35 ± 0.05 μM L-DOPA Noncompetitive [ 67 ] In2 (Capsaicin) 0.79 ± 0.011 mM Competitive In3 (Dihydrocapsaicin) 1.37 ± 0.16 mM Mixed type [ 68 ] In4 (Caffeine) 18.5 ± 23.1 μg/mL Noncompetitive [ 47 ] In5 (Caftaric acid) 30 μM Competitive [ 48 ] In6 (Phloretin) 169.36 μM Mixed type [ 49 ] In7 (AMTAC-01) 189.40 μM Noncompetitive In8 (AMTAC-02) 96.29 μM Mixed type [ 69 ] In9 (TSC-6) 0.5 μM Competitive In10 (TSC-12) 0.9 μM Competitive In11 (TSC-21) 0.8 μM Competitive [ 70 ] In12 (Penicillin V) 16.6 ± 0.5 mM monophenolase Mi...…”

Section: Inhibitors Of Tyrosinasementioning

confidence: 99%

“…It was found that TSCs 6, 12, and 21 ( In9/10/11 , Fig. 9 [ 69 ]) exhibit the potent inhibitory properties with different IC50, respectively ( Table 1 ). They demonstrate a mutually reversible and competitive mechanism to inhibit tyrosinase.…”

Section: Inhibitors Of Tyrosinasementioning

confidence: 99%

See 1 more Smart Citation

Catalysis-based specific detection and inhibition of tyrosinase and their application

et al. 2020

Journal of Pharmaceutical Analysis

View full text Add to dashboard Cite

Tyrosinase is an important enzyme in controlling the formation of melanin in melanosome, and plays a key role in the pigmentation of hair and skin. The abnormal expression or activation of tyrosinase is associated with several diseases such as albinism, vitiligo, melanoma and Parkinson disease. Excessive deposition of melanin could cause diseases such as freckles and brown spots in the human body, and it is also closely related to browning of fruits and vegetables and insect molting. Detecting and inhibiting the activity of tyrosinase is of extraordinary value in the progress of diagnosis and treatment of these diseases. Therefore, many selective optical detection probes and small molecular inhibitors have been developed, and have made significant contributions to the basic and clinical research on these diseases. In this paper, the detection and inhibition of tyrosinase and their application in whitening products are reviewed, with special emphasis on development of fluorescent probes and inhibitors. Hopefully, this review will help design more efficient and sensitive tyrosinase probes and inhibitors, as well as shed light on novel treatment of diseases such as melanoma.

show abstract

“…[30][31][32][33]. In addition, thiosemicarbazones (TSCs) have a wide clinical antitumor spectrum with efficacy in various tumor types such as bladder cancer, pancreatic cancer, cervical cancer, non-small cell lung cancer, breast cancer, prostate cancer and leukemia [34][35][36][37]. Figure 3 shows some representative compounds with thiosemicarbazones structure in the clinical trial.…”

Section: Introductionmentioning

confidence: 99%

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Wang

et al. 2020

Molecules

View full text Add to dashboard Cite

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

show abstract

Halogenated aromatic thiosemicarbazones as potent inhibitors of tyrosinase and melanogenesis

Cited by 25 publications

References 58 publications

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

4‐Fluorobenzylpiperazine‐Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

Catalysis-based specific detection and inhibition of tyrosinase and their application

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Contact Info

Product

Resources

About