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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

Author(s): Hatem A. Abuelizz, El Hassane Anouar, Mohamed Marzouk, Mizaton H. Hasan, Siti R. Saleh, Adi Ahudhaif, Khalid A. Alburikan and Rashad Al-Salahi*

Volume 20 , Issue 14 , 2020

Page: [1714 - 1721] Pages: 8

DOI: 10.2174/1871520620666200627212128

Price: $65

Abstract

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies.

Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines.

Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets.

Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase.

Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Keywords: Pyridotriazolopyrimidine, tyrosinase inhibition, cytotoxicity, molecular docking, HepG2, MCF-7.

Graphical Abstract
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