Abstract
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 = 11.5 µM) 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.
Highlights
Out of several green chemistry methodologies, one simple and rapid methodology to prepare chemical and pharmaceutical compounds is via grindstone chemistry
This study focused on naphtho[2,3-g]phthalazine models covered by anthraquinone analogues in order to analyze the effect of antityrosinase activity
We studied a new naphtho[2,3-g]phthalazine core belonging to the group of anthraquinone derivatives, and evaluated their anti-tyrosinase activity in vitro
Summary
Out of several green chemistry methodologies, one simple and rapid methodology to prepare chemical and pharmaceutical compounds is via grindstone chemistry. Some of the known green trends in the Mannich reaction include ball-milling solvent-free [4], or with ionic liquid medium [5], nanoparticles [6], or enzymes in bio-catalytic conditions [7,8]. These green trends in the Mannich reaction suffer with the challenges outlined above. Based on the above observations, the tyrosinase inhibitory activities of naphtho[2,3-g]phthalazine derivatives have not been previously studied. We studied a new naphtho[2,3-g]phthalazine core belonging to the group of anthraquinone derivatives, and evaluated their anti-tyrosinase activity in vitro. Our kinetic studies allowed us to discuss and compare molecular docking results compared with wet lab results
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