Tel-Cu-NPs Catalyst: Synthesis of Naphtho[2,3-g]phthalazine Derivatives as Potential Inhibiters of Tyrosinase Enzymes and Their Investigation in Kinetic, Molecular Docking, and Cytotoxicity Studies

Catalysts

Saud Alarifi¹  Ali Daoud¹  Akbar Idhayadhulla²  Keerthana Selvaraj² 

[1] Department of Zoology, College of Sciences, King Saud University (KSU), P.O. Box 2455, Riyadh 11451, Saudi Arabia;Research Department of Chemistry, Nehru Memorial College (Affiliated to Bharathidasan University), Puthanampatti 621007, Tiruchirappalli District, Tamil Nadu, India;

关键词: Tel-Cu-Nps catalyst;    naphtho[2,3-g]phthalazine;    kojic acid;    mushroom tyrosinase;    molecular docking, kinetic behaviour;    cytotoxicity activity;   

DOI  :  10.3390/catal10121442

来源: DOAJ

【 摘 要 】

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized compounds, along with analysis of kinetic behavior and molecular docking studies. The synthesized compound, 1c was (IC₅₀=11.5µM) more active than kojic acid (IC₅₀= 78.0 µM). Lineweaver Burk plots were used to analyze the kinetic behavior of the most active compound 1c, it was reversible and competitive behavior. Compound 1c and kojic acid occurred in the presence of 2-hydroxyketone, which has the same inhibitory mechanism. The molecular docking of compound 1c and the control kojic acid were docked against 2Y9X protein via the Schrodinger Suite. The compound 1c showed a respectable dock score (−5.6 kcal/mol) compared to kojic acid with a dock score of (−5.2 kcal/mol) in the 2Y9X protein. Cytotoxicity activity was also evaluated by using HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines, and high activity for 1c (GI₅₀ = 0.01, 0.03, and 0.04 µM, respectively) against all cell lines was found compared to standard and other compounds. Therefore, this study succeeded in testing a few promising molecules as potential antityrosinase agents.

【 授权许可】

Unknown