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

Mohd Aluwi, Mohd Fadhlizil Fasihi and Rullah, Kamal and Tan, Huan Huan and Chan, Kok Meng and Tan, Si Jie and Leong, Sze Wei and Mansor, Ahmad Hasnan and Yamin, Bohari M. and Lam, Kok Wai (2016) Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells. RSC Advances, 6 (76). pp. 72177-72184. ISSN 2046-2069

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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 mM, 27.42 mM and 32.51 mM, respectively. Further kinetic studies revealed that compounds 1 (Ki ¼ 3.8 mM) and 3 (Ki ¼ 3.9 mM) exhibited a mixed-type inhibition while compound 2 (Ki ¼ 0.7 mM) 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 mM treatment via MTT assay.

Item Type: Article (Journal)
Additional Information: 9020/73761
Uncontrolled Keywords: Dynamics simulation, Epidermal melanin, Lineweaver-Burk plots, Low cytotoxicities, Malignant melanoma, Molecular docking, Mushroom tyrosinase, Oxadiazole derivatives
Subjects: R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy
Depositing User: Dr Kamal Rullah
Date Deposited: 17 Sep 2019 16:17
Last Modified: 17 Sep 2019 16:17
URI: http://irep.iium.edu.my/id/eprint/73761

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