Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

Zaman Ashraf, Muhammad Rafiq, Humaira Nadeem, Mubashir Hassan, Samina Afzal, Muhammad Waseem, Khurram Afzal, Jalifah Latip

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity. The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy). Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69|JM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively. Lineweaver - Burkand Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Kivalues19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase. The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others. The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings. Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.

Original languageEnglish
Article numbere0178069
JournalPLoS One
Volume12
Issue number5
DOIs
Publication statusPublished - 1 May 2017

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Monophenol Monooxygenase
carvacrol
Agaricales
mushrooms
inhibitory concentration 50
chemical derivatives
kojic acid
Derivatives
kinetics
Inhibitory Concentration 50
synthesis
enzyme inhibitors
benzoic acid
cosmetics
binding sites
Enzyme kinetics
Benzoic Acid
Cosmetics
Enzyme Inhibitors
mass spectrometry

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies. / Ashraf, Zaman; Rafiq, Muhammad; Nadeem, Humaira; Hassan, Mubashir; Afzal, Samina; Waseem, Muhammad; Afzal, Khurram; Latip, Jalifah.

In: PLoS One, Vol. 12, No. 5, e0178069, 01.05.2017.

Research output: Contribution to journalArticle

Ashraf, Zaman ; Rafiq, Muhammad ; Nadeem, Humaira ; Hassan, Mubashir ; Afzal, Samina ; Waseem, Muhammad ; Afzal, Khurram ; Latip, Jalifah. / Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies. In: PLoS One. 2017 ; Vol. 12, No. 5.
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