Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells

Mohd Fadhlizil Fasihi Mohd Aluwi, Kamal Rullah, Tan Huan Huan, Chan Kok Meng, Tan Si Jie, Leong Sze Wei, Ahmad Hasnan Mansor, Bohari Mohd. Yamin, Kok Wai Lam

Research output: Contribution to journalArticle

Abstract

Melanin is a form of pigment that gives colour to human skin, hair and eyes. Whilst it protects against skin damage from the sun, accumulation of excessive amounts of epidermal melanin can lead to various dermatological disorders. This study aimed to evaluate the effects of three selected oxadiazoles on the o-diphenolase mushroom tyrosinase activity and their cytotoxic effects on SK-MEL-28 malignant melanoma cells. The results showed that compounds 1, 2 and 3 exhibited significant inhibition on the diphenolase activity of mushroom tyrosinase with IC50 values of 40.46 μM, 27.42 μM and 32.51 μM, respectively. Further kinetic studies revealed that compounds 1 (Ki = 3.8 μM) and 3 (Ki = 3.9 μM) exhibited a mixed-type inhibition while compound 2 (Ki = 0.7 μM) displayed a competitive-type inhibition as suggested by the Lineweaver-Burk plots. Molecular docking and dynamics simulations were also performed to understand the binding behaviour of compound 2 in the active site of tyrosinase. Finally, all three compounds displayed relatively low cytotoxicity to SK-MEL-28 cells up to 100 μM treatment via MTT assay.

Original languageEnglish
Pages (from-to)72177-72184
Number of pages8
JournalRSC Advances
Volume6
Issue number76
DOIs
Publication statusPublished - 2016

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Melanin
Oxadiazoles
Monophenol Monooxygenase
Skin
Melanins
Derivatives
Cytotoxicity
Pigments
Sun
Assays
Color
Kinetics
Computer simulation

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

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Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells. / Fasihi Mohd Aluwi, Mohd Fadhlizil; Rullah, Kamal; Huan, Tan Huan; Kok Meng, Chan; Jie, Tan Si; Wei, Leong Sze; Mansor, Ahmad Hasnan; Mohd. Yamin, Bohari; Lam, Kok Wai.

In: RSC Advances, Vol. 6, No. 76, 2016, p. 72177-72184.

Research output: Contribution to journalArticle

Fasihi Mohd Aluwi, MF, Rullah, K, Huan, TH, Kok Meng, C, Jie, TS, Wei, LS, Mansor, AH, Mohd. Yamin, B & Lam, KW 2016, 'Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells', RSC Advances, vol. 6, no. 76, pp. 72177-72184. https://doi.org/10.1039/c6ra12754a
Fasihi Mohd Aluwi, Mohd Fadhlizil ; Rullah, Kamal ; Huan, Tan Huan ; Kok Meng, Chan ; Jie, Tan Si ; Wei, Leong Sze ; Mansor, Ahmad Hasnan ; Mohd. Yamin, Bohari ; Lam, Kok Wai. / Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells. In: RSC Advances. 2016 ; Vol. 6, No. 76. pp. 72177-72184.
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