Design, synthesis and biological evaluation of oxindole-based chalcones as small-molecule inhibitors of melanogenic tyrosinase

Sharad Kumar Suthar, Sumit Bansal, Niteen Narkhede, Manju Guleria, Angel Treasa Alex, Alex Joseph

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihy-droxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-based chalcones as monophenolase and diphenolase activity inhibitors of tyrosinase. Among the screened compounds, 4-hydroxy-3-methoxybenzylidene moiety bearing chalcone (7) prepared by one pot reaction of oxindole and vanillin displayed the highest activity against tyrosinase with IC50s of 63.37 and 59.71µM in monophenolase and diphenolase activity assays, respectively. In molecular docking studies, chalcone 7 also showed the highest binding affinity towards the enzyme tyrosinase while exhibiting the lowest estimated free energy of binding, among all the ligands docked.

Original languageEnglish
Pages (from-to)833-839
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume65
Issue number9
DOIs
Publication statusPublished - 2017

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Chalcones
Monophenol Monooxygenase
Chalcone
Molecules
Bearings (structural)
Hyperpigmentation
Biosynthesis
Melanins
Enzymes
Free energy
Assays
Skin
Ligands
oxindole
monophenolase

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

Cite this

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title = "Design, synthesis and biological evaluation of oxindole-based chalcones as small-molecule inhibitors of melanogenic tyrosinase",
abstract = "The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihy-droxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-based chalcones as monophenolase and diphenolase activity inhibitors of tyrosinase. Among the screened compounds, 4-hydroxy-3-methoxybenzylidene moiety bearing chalcone (7) prepared by one pot reaction of oxindole and vanillin displayed the highest activity against tyrosinase with IC50s of 63.37 and 59.71µM in monophenolase and diphenolase activity assays, respectively. In molecular docking studies, chalcone 7 also showed the highest binding affinity towards the enzyme tyrosinase while exhibiting the lowest estimated free energy of binding, among all the ligands docked.",
author = "Suthar, {Sharad Kumar} and Sumit Bansal and Niteen Narkhede and Manju Guleria and Alex, {Angel Treasa} and Alex Joseph",
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Design, synthesis and biological evaluation of oxindole-based chalcones as small-molecule inhibitors of melanogenic tyrosinase. / Suthar, Sharad Kumar; Bansal, Sumit; Narkhede, Niteen; Guleria, Manju; Alex, Angel Treasa; Joseph, Alex.

In: Chemical and Pharmaceutical Bulletin, Vol. 65, No. 9, 2017, p. 833-839.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Design, synthesis and biological evaluation of oxindole-based chalcones as small-molecule inhibitors of melanogenic tyrosinase

AU - Suthar, Sharad Kumar

AU - Bansal, Sumit

AU - Narkhede, Niteen

AU - Guleria, Manju

AU - Alex, Angel Treasa

AU - Joseph, Alex

PY - 2017

Y1 - 2017

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AB - The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihy-droxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-based chalcones as monophenolase and diphenolase activity inhibitors of tyrosinase. Among the screened compounds, 4-hydroxy-3-methoxybenzylidene moiety bearing chalcone (7) prepared by one pot reaction of oxindole and vanillin displayed the highest activity against tyrosinase with IC50s of 63.37 and 59.71µM in monophenolase and diphenolase activity assays, respectively. In molecular docking studies, chalcone 7 also showed the highest binding affinity towards the enzyme tyrosinase while exhibiting the lowest estimated free energy of binding, among all the ligands docked.

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