Design, Synthesis, and Molecular Dynamics Simulation Studies of New Chalcone‐Based 2‐Arylidene‐1,3‐indandiones as Tyrosinase Inhibitors

Najafi, Zahra; Rafiei, Farshideh; Ghafouri‐Khosrowshahi, Abolfazl; Mahdavi, Mohammad; Dianatpour, Mehdi; Iraji, Aida

doi:10.1002/slct.202302192

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…Melanin, as a crucial biopolymer, is produced by melanocytes and is responsible for eye, skin, and hair color [1][2][3]. One important role of melanin is to protect the skin against ultraviolet damage [4][5][6]. Excessive ultraviolet exposure typically leads to abnormal melanin production and deposition, which generally results in several pigmentation skin diseases, including lentigo, freckles, and melisma [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

Lu,

Hu,

Min

et al. 2023

Molecules

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Tyrosinase is an important rate-limiting enzyme in melanin biosynthesis. To find potential tyrosinase inhibitors with anti-melanogenic activity, a series of indole-thiazolidine-2,4-dione derivatives 5a~5z were synthesized by incorporating indole with thiazolidine-2,4-dione into one compound and assayed for their biological activities. All compounds displayed tyrosinase inhibitory activities and 5w had the highest anti-tyrosinase inhibitory activity with an IC50 value of 11.2 μM. Inhibition kinetics revealed 5w as a mixed-type tyrosinase inhibitor. Fluorescence quenching results indicated that 5w quenched tyrosinase fluorescence in a static process. CD spectra and 3D fluorescence spectra results suggested that the binding of 5w with tyrosinase could change the conformation and microenvironment of tyrosinase. Molecular docking also represented the binding between 5w and tyrosinase. Moreover, 5w could inhibit tyrosinase activity and melanogenesis both in B16F10 cells and the zebrafish model. Therefore, compound 5w could serve as a tyrosinase inhibitor with anti-melanogenic activity.

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Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

Lu,

Hu,

Min

et al. 2023

Molecules

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Design, synthesis, QSAR modelling and molecular dynamic simulations of N-tosyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors

Batool,

Ullah,

Khan

et al. 2024

Sci Rep

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Tyrosinase is an enzyme crucial for the progression of melanogenesis. Immoderate production of melanin may be the cause of hyperpigmentation and darkening leading to skin diseases. Tyrosinase is the most researched target for suppressing melanogenesis since it catalyzes the rate-limiting stage of melanin production. Thiosemicarbazones have been reported to possess strong inhibition capability against tyrosinase. We have designed and synthesized eighteen N-tosyl substituted indole-based thiosemicarbazones as competitive tyrosinase inhibitors in the current work. All the compounds exhibited outstanding to good potency with half maximal inhibitory concentration in the range of 6.40 ± 0.21 µM to 61.84 ± 1.47 µM. The compound 5r displayed the top-tier inhibition amongst the entire series with IC 50 = 6.40 ± 0.21 µM. Compounds, 5q and 5r exhibited competitive inhibitions in concentration dependent manner with Ki = 3.42 ± 0.03 and 10.25 ± 0.08 µM respectively. The binding mode of 5r was evaluated through in silico molecular dynamics simulations and molecular docking, while ADME assessment studies predicted the drug-like characteristics of the derivatives. The newly synthesized derivatives may serve as a structural guide for designing and developing novel tyrosinase inhibitors. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-75100-1.

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Organocatalyzed Enantioselective [3+2] Cycloaddition Reactions for Synthesis of Dispiro[benzothiophenone-indandione-pyrrolidine] Derivatives

Liu,

2024

Molecules

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An organocatalytic enantioselective [3+2] cycloaddition reaction involving 2-arylidene-1,3-indandiones and N-2,2-difluoroethylbenzothiophenone imines was developed. This approach efficiently afforded dispiro[benzothiophenone-indandione-pyrrolidine]s, featuring three stereocenters, in 84–98% yields with 3–93% ee and 9:1–>20:1 dr. Notably, the method maintained its yield and enantioselectivity integrity even in a gram-scale amplification experiment. For example, the product with substituents on aromatics were obtained in 90% yield with 91% ee and >20:1 dr. Its absolute configuration was established through X-ray single-crystal diffraction analysis, and a plausible reaction mechanism was proposed.

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Design, Synthesis, and Molecular Dynamics Simulation Studies of New Chalcone‐Based 2‐Arylidene‐1,3‐indandiones as Tyrosinase Inhibitors

Cited by 3 publications

References 28 publications

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

Design, synthesis, QSAR modelling and molecular dynamic simulations of N-tosyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors

Organocatalyzed Enantioselective [3+2] Cycloaddition Reactions for Synthesis of Dispiro[benzothiophenone-indandione-pyrrolidine] Derivatives

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