Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid

Pervaiz Ali Channar; Aamer Saeed; Fayaz Ali Larik; Bakhtawar Batool; Saima Kalsoom; M M Hasan; Mauricio F Erben; Hesham R El-Seedi; Musrat Ali; Zaman Ashraf

doi:10.1016/j.bioorg.2018.04.026

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid

Bioorg Chem. 2018 Sep:79:293-300. doi: 10.1016/j.bioorg.2018.04.026. Epub 2018 Apr 30.

Authors

Affiliations

¹ Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
² Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan. Electronic address: aamersaeed@yahoo.com.
³ Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan. Electronic address: fayazali@chem.qau.edu.pk.
⁴ SA-CIRBS, International Islamic University, Islamabad, Pakistan.
⁵ Pakistan Institute of Engineering and Applied Sciences, PIEAS, Pakistan.
⁶ CEQUINOR (UNLP, CONICET-CCT La Plata), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 962, La Plata 1900, Argentina.
⁷ Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden.
⁸ Department of Biological Sciences, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
⁹ Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan.

PMID: 29793142
DOI: 10.1016/j.bioorg.2018.04.026

Abstract

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC₅₀ = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC₅₀ = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.

Keywords: Aryl pyrazoles; In silico Molecular docking studies; In vitro Mushroom tyrosinase assay; Kojic acid; Suzuki cross coupling.

Publication types

Comparative Study

MeSH terms

Agaricales / enzymology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Kinetics
Molecular Docking Simulation*
Molecular Structure
Monophenol Monooxygenase / antagonists & inhibitors*
Monophenol Monooxygenase / metabolism
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrones / chemistry
Pyrones / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Pyrazoles
Pyrones
kojic acid
Monophenol Monooxygenase