Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors

Kok Wai Lam, Ahmad Syahida, Zaheer Ul-Haq, Mohd Basyaruddin Abdul Rahman, Nordin H. Lajis

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A series of 16 oxadiazole and triazolothiadiazole derivatives were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. Five derivatives were found to display high inhibition on the tyrosinase activity ranging from 0.87 to 1.49 μM. Compound 5 exhibited highest tyrosinase inhibitory activity with an IC50 value of 0.87 ± 0.16 μM. The in silico protein-ligand docking using autodock 4.1 was successfully performed on compound 5 with significant binding energy value of -5.58 kcal/mol. The docking results also showed that the tyrosinase inhibition might be due to the metal chelating effect by the presence of thione functionality in compounds 1-5. Further studies revealed that the presence of hydrophobic group such as cycloamine derivatives played a major role in the inhibition. Piperazine moiety in compound 5 appeared to be involved in an extensive hydrophobic contact and a 2.9 hydrogen bonding with residue Glu 182 in the active site.

Original languageEnglish
Pages (from-to)3755-3759
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number12
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Oxadiazoles
Monophenol Monooxygenase
Bioactivity
Derivatives
Thiones
Agaricales
Hydrogen Bonding
Chelation
Binding energy
Computer Simulation
Inhibitory Concentration 50
Catalytic Domain
Hydrogen bonds
Metals
Ligands
Proteins

Keywords

  • Mushroom tyrosinase inhibitor
  • Oxadiazole
  • Piperazine
  • Triazolothiadiazole

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors. / Lam, Kok Wai; Syahida, Ahmad; Ul-Haq, Zaheer; Rahman, Mohd Basyaruddin Abdul; Lajis, Nordin H.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 12, 2010, p. 3755-3759.

Research output: Contribution to journalArticle

Lam, Kok Wai ; Syahida, Ahmad ; Ul-Haq, Zaheer ; Rahman, Mohd Basyaruddin Abdul ; Lajis, Nordin H. / Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 12. pp. 3755-3759.
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