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*   Pages 1714 - 1721 ( 8 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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. </P><P> Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.</P>

Keywords:

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

Affiliation:

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-kharj 11942, Department of Tanning Materials and Leather Technology, Chemistry of Natural Products Group (Center of Excellence for Advanced Sciences), National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.), Dokki, Cairo 12622, Department of Pharmaceutical Chemistry and Pharmacology, Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor, Department of Pharmaceutical Chemistry and Pharmacology, Faculty of Pharmacy, Campus Puncak Alam, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor, Department of Computer Science, College of Computer Engineering and Sciences in Al-kharj, Prince Sattam bin Abdulaziz University, P.O. Box 151, Al-kharj 11942, Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451

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