Novel 1,3,4-oxadiazole compounds inhibit the tyrosinase and melanin level: Synthesis, in-vitro, and in-silico studies

• Published in: Bioorganic & medicinal chemistry Vol. 41; pp. 116222 - 116234
• Main Authors: Vanjare, Balasaheb D., Choi, Nam Gyu, Mahajan, Prasad G., Raza, Hussain, Hassan, Mubashir, Han, Yohan, Yu, Seon-Mi, Kim, Song Ja, Seo, Sung-Yum, Lee, Ki Hwan
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2021; Elsevier
• Subjects: 1,3,4-oxadiazole; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytotoxicity; Dynamic simulation; Life Sciences & Biomedicine; Melanin content; Molecular docking; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Tyrosinase inhibitor; Melanin content; Cytotoxicity; Dynamic simulation; Tyrosinase inhibitor; 1,3,4-oxadiazole; Molecular docking; 1; 3; 4-oxadiazole; BIOLOGICAL EVALUATION; DERIVATIVES
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2021.116222

[Display omitted] •A series of the 1,3,4-oxadiazole based derivatives were synthesized.•All the oxadiazole compounds demonstrate good tyrosinase inhibitory activity.•Among the series, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)-N-phenylacetamide exhibit more potent activity than standard drug.•Most potent compound exhibit non-toxic behavior against B16F10 melanoma cells.•The in-vitro results are in support of molecular docking studies. In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, 1H NMR and 13C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed. The in-vitro study reveals that, all compounds demonstrate an excellent tyrosinase inhibitory activity. Especially, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)-N-phenylacetamide (IC50 = 0.003 ± 0.00 µM) confirms much more significant potent inhibition activity compared with standard drug kojic acid (IC50 = 16.83 ± 1.16 µM). Subsequently, the most potent five oxadiazole compounds were screened for cytotoxicity study against B16F10 melanoma cells using an MTT assay method. The survival rate for the most potent compound was more pleasant than other compounds. Furthermore, the western blot results proved that the most potent compound considerably decreased the expression level of tyrosinase at 50 µM (P < 0.05). The molecular docking investigation exposed that the utmost potent compound displayed the significant interactions pattern within the active region of the tyrosinase enzyme and which might be responsible for the decent inhibitory activity towards the enzyme. A molecular dynamic simulation experiment was presented to recognize the residual backbone stability of protein structure.