Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors

Ujan, Rabail; Saeed, Aamer; Ashraf, Saba; Channar, Pervaiz Ali; Abbas, Qamar; Rind, Mahboob Ali; Hassan, Mubashir; Raza, Hussain; Seo, Sung‐Yum; El‐Seedi, Hesham R.

doi:10.1080/07391102.2020.1804459

Cited by 12 publications

(19 citation statements)

References 29 publications

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“…Of the 13 synthesized compounds, three exhibited potent tyrosinase inhibitor; 1 (IC 50 = 3.70 µM) with a 4-hydroxy substituent; 2 (IC 50 = 3.05 µM) with a 3,4-dihydroxy substituent; and 3 (IC 50 = 5.00 µM) with a 2,4-dihydroxy substituent. Specifically, the inhibitory potencies of compounds 1, 2, and 3 were 4.9-, 6.0-, and 3.7-fold greater, respectively, than those of kojic acid (IC 50 hydroxyl group on the β-phenyl ring showed weak or no inhibition. The 3-methoxy-4hydroxy group of the β-phenyl ring increased tyrosinase inhibitory activity compared to the 3-hydroxy-4-methoxy group of the β-phenyl ring (compounds 4 vs. 6).…”

Section: Inhibitory Activities Of (Z)-2-(substituted Benzylidene)benzimidazothiazolone Derivatives 1-13 Against Mushroom Tyrosinasementioning

confidence: 97%

“…The most important factor involved in tyrosinase inhibition are coordinated with Cu ions, which played an important role in the activity. The binding energy, number of interaction residues of the compounds, and the reference compound kojic acid (competitive inhibitor) (Figure 3B) [49,50] are summarized in Table 4 and Figure 3A. The most potent compound 2 was stabilized by HIS85-, HIS244-, ASN260-, HIS263-, PHE264-, MET280-, GLY281-, SER282-, VAL283-, and GLU322-interacting (hydrogen/hydrophobic) residues (Figure 3D,G).…”

Section: Docking Simulation and Of Ligands Against Tyrosinasementioning

confidence: 99%

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New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities

et al. 2021

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Thirteen (Z)-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1–3 showed greater inhibitory activity than kojic acid (IC50 = 18.27 ± 0.89 μM); IC50 = 3.70 ± 0.51 μM for 1; IC50 = 3.05 ± 0.95 μM for 2; and IC50 = 5.00 ± 0.38 μM for 3, and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1–3 could bind to the catalytic sites of tyrosinase. Compounds 1–3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

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Section: Inhibitory Activities Of (Z)-2-(substituted Benzylidene)benzimidazothiazolone Derivatives 1-13 Against Mushroom Tyrosinasementioning

confidence: 97%

Section: Docking Simulation and Of Ligands Against Tyrosinasementioning

confidence: 99%

New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities

et al. 2021

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“…Although using the tyrosinase enzyme extracted from a mushroom for an in vitro tyrosinase inhibitory assay has been widely studied as a routine screening for tyrosinase inhibition [19], tyrosinase from the mushroom is located in the cytoplasm and is different from the mammalian tyrosinase that is found on the membrane of melanocytes [20]. Therefore, cell-based assays are also usually utilized to identify the potential tyrosinase inhibitor.…”

Section: Targeted-proteomics Analysis Of the Octapeptide In Melanoma ...mentioning

confidence: 99%

Discovery of a Multifunctional Octapeptide from Lingzhi with Antioxidant and Tyrosinase Inhibitory Activity

et al. 2022

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Ganoderma lucidum or Lingzhi is a fungus species widely known as a traditional medicine. Exploring the beneficial peptides by hydrolysis using pepsin and trypsin has been extensively performed to identify new bioactive natural products. A multifunctional peptide that expresses potential scavenging activity and tyrosinase inhibition is valuable in therapeutic and cosmetic applications. This study aimed to identify and investigate the effects of a novel multifunctional peptide from Lingzhi on the melanogenic enzymes in melanoma cells by a targeted-proteomics approach. The multifunctional peptide was de novo sequenced by LC-MS/MS to be NH2-PVRSSNCA-CO2H (octapeptide). This sequence was chemically synthesized by solid-phase peptide synthesis (SPPS). The antioxidant ability of the synthesized octapeptide was measured by the DPPH, ABTS, and FRAP assays. The results showed that the peptide exhibited an antioxidant activity equal to 0.121 ± 0.01 mg equivalent to ascorbic acid, 0.173 ± 0.03 mg equivalent to gallic acid, and 2.21 ± 0.23 mM equivalent to FeSO4, respectively, which is comparable to these well-known antioxidants. The proteomics approach identified a total of 5804 proteins and several pathways involved in the effects of the octapeptide in melanoma cells. Targeted proteomics revealed three specific proteins associated with pigmentation including Rab29, Dct, and Tyrp1. The Rab29 and Dct were upregulated whereas Tyrp1 was downregulated in the octapeptide treatment group. These findings could be used in the understanding of the molecular functions of the multifunctional octapeptide on melanogenic enzymes, supporting its potential as a therapeutic and cosmetic ingredient.

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“…Benzothiazoles exhibit comprehensive spectrum of bioactivities, including anticancer, 7 antibacterial, 8 antifungal, 9,10 anti-inflammatory, 11,12 antioxidant, 13 antiviral, 14 anti-HIV-1, 15 and enzyme inhibitor. 16 On the other hand, chalcones have been known as naturally occurring compounds that have a wide biological spectrum and various applications for essential fields. Natural chalcones and their synthetic analogs have been shown to have a wide range of biological effects including anticancer, 17 antioxidant, 18 antibacterial/antifungal, 19 anti-inflammatory, 20 antimalarial, 21 antileishmanial, 22 enzyme inhibitory, 23 and so forth.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, enzyme inhibition, and molecular docking studies of a novel chalcone series bearing benzothiazole scaffold

Musatat

Atahan

Ergün

et al. 2023

Biotech and App Biochem

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This study reports the facile synthesis of a novel series of benzothiazole‐chalcones, in addition to their inhibitory profile on important metabolic enzymes including human carbonic anhydrases (hCA‐I, hCA‐II) and paraoxonase (PON‐1). The inhibition parameters, IC50 (concentration for 50% inhibition) and Ki (dissociation constant) values, toward the title enzymes were determined for the studied compounds. As a result, IC50 values of hydratase activity were in the range 4.15–5.47 and 2.56–4.58 μM for hCA‐I and hCA‐II, respectively. At the same time, IC50 values of esterase activity were in the range 24.91–104.00 and 35.25–97.00 μM, while Ki values were in the range 14.43–59.66 and 26.65–73.34 μM for hCA‐I and hCA‐II, respectively. In addition, PON‐1 enzyme inhibition results showed interesting inhibitory effects, with IC50 values between 13.28 and 16.68 μM. Finally, a comprehensive approach was established for the synthesized compounds based on theoretical calculations, which have been done using B3LYP, PBE0 theories and SVP, TVZP, TVZPP basis sets, followed by docking studies by which the outputs proved the harmonically flows with the experimental results.

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Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors

Cited by 12 publications

References 29 publications

New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities

New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities

Discovery of a Multifunctional Octapeptide from Lingzhi with Antioxidant and Tyrosinase Inhibitory Activity

Synthesis, enzyme inhibition, and molecular docking studies of a novel chalcone series bearing benzothiazole scaffold

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