Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors
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 lM. Compound 5 exhibited highest tyrosinase inhibitor...
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| Format: | Article |
| Language: | English |
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Elsevier
2010
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| Online Access: | http://psasir.upm.edu.my/id/eprint/16919/ http://psasir.upm.edu.my/id/eprint/16919/1/Synthesis%20and%20biological%20activity%20of%20oxadiazole%20and%20triazolothiadiazole%20derivatives%20as%20tyrosinase%20inhibitors.pdf |
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| author | Lam, Kok Wai Ahmad, Syahida Ul-Haq, Zaheer Abdul Rahman, Mohd Basyaruddin Lajis, Nordin |
| author_facet | Lam, Kok Wai Ahmad, Syahida Ul-Haq, Zaheer Abdul Rahman, Mohd Basyaruddin Lajis, Nordin |
| author_sort | Lam, Kok Wai |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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 lM. Compound 5 exhibited highest tyrosinase inhibitory activity with an IC50 value of 0.87 ± 0.16 lM. 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 Å hydrogen bonding with residue Glu 182 in the active site. |
| first_indexed | 2025-11-15T08:09:36Z |
| format | Article |
| id | upm-16919 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T08:09:36Z |
| publishDate | 2010 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-169192016-09-02T09:35:44Z http://psasir.upm.edu.my/id/eprint/16919/ Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors Lam, Kok Wai Ahmad, Syahida Ul-Haq, Zaheer Abdul Rahman, Mohd Basyaruddin Lajis, Nordin 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 lM. Compound 5 exhibited highest tyrosinase inhibitory activity with an IC50 value of 0.87 ± 0.16 lM. 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 Å hydrogen bonding with residue Glu 182 in the active site. Elsevier 2010 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/16919/1/Synthesis%20and%20biological%20activity%20of%20oxadiazole%20and%20triazolothiadiazole%20derivatives%20as%20tyrosinase%20inhibitors.pdf Lam, Kok Wai and Ahmad, Syahida and Ul-Haq, Zaheer and Abdul Rahman, Mohd Basyaruddin and Lajis, Nordin (2010) Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors. Bioorganic & Medicinal Chemistry Letters, 20 (12). pp. 3755-3759. ISSN 0960-894X; ESSN: 1464-3405 10.1016/j.bmcl.2010.04.067 |
| spellingShingle | Lam, Kok Wai Ahmad, Syahida Ul-Haq, Zaheer Abdul Rahman, Mohd Basyaruddin Lajis, Nordin Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title | Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title_full | Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title_fullStr | Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title_full_unstemmed | Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title_short | Synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| title_sort | synthesis and biological activity of oxadiazole and triazolothiadiazole derivatives as tyrosinase inhibitors |
| url | http://psasir.upm.edu.my/id/eprint/16919/ http://psasir.upm.edu.my/id/eprint/16919/ http://psasir.upm.edu.my/id/eprint/16919/1/Synthesis%20and%20biological%20activity%20of%20oxadiazole%20and%20triazolothiadiazole%20derivatives%20as%20tyrosinase%20inhibitors.pdf |