Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells
| Autor: | Mohd Fadhlizil Fasihi Mohd Aluwi, Kamal Rullah, Tan Huan Huan, Leong Sze Wei, Tan Si Jie, Chan Kok Meng, Lam Kok Wai, Bohari Mohd. Yamin, Ahmad Hasnan Mansor |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
integumentary system 010304 chemical physics biology General Chemical Engineering Melanoma Tyrosinase Oxadiazole Active site Human skin General Chemistry medicine.disease 01 natural sciences Melanin 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Biochemistry 0103 physical sciences medicine biology.protein MTT assay Cytotoxicity |
| Zdroj: | RSC Advances. 6:72177-72184 |
| ISSN: | 2046-2069 |
| DOI: | 10.1039/c6ra12754a |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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