Sains Malaysiana 50(9)(2021): 2603-2614

http://doi.org/10.17576/jsm-2021-5009-09

Synthesis, Molecular Docking and Tyrosinase Inhibitory Activity of the Decorated Methoxy Sulfonamide Chalcones:  in vitro Inhibitory Effects and the Possible Binding Mode

(Sintesis, Penyambungan Molekul dan Aktiviti Perencatan Tirosinase dari Metoksi Sulfonamida Kalkon: Kesan Perencatan in vitro dan Mod Pengikatan Mungkin)

THAWANRAT KOBKEATTHAWIN¹, SUCHADA CHANTRAPROMMA¹*, THITIPONE SUWUNWONG², LYDIA RHYMAN^3,4, YEE SIEW CHOONG⁵ & PONNADURAI RAMASAMI^3,4

¹Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand

²School of Science, Mae Fah Luang University, Chiang Rai 57100, Thailand  

³Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius

⁴Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg
Doornfontein Campus, Johannesburg 2028, South Africa

⁵Computational Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM 11800, Malaysia 

Received: 17 May 2020/Accepted: 13 January 2021

ABSTRACT

In this study, a series of sulfonamide chalcones derivatives was synthesized and its chemical structures were confirmed by spectral characteristics. The synthesized compounds were evaluated for their tyrosinase inhibitory activities along with molecular docking study. The tyrosinase inhibitory results indicated that compounds 5b, 5c, 5f, 5g and 5h displayed the significant tyrosinase inhibitory activity and comparable to the standard drug (kojic acid). Compound 5c exhibits the most potent tyrosinase inhibition among the synthesized compounds with IC₅₀ = 0.43±0.07 mM, L-DOPA as the substrate, and better than that of the standard kojic acid (IC₅₀ = 0.60±0.20 mM). Molecular docking studies showed that the binding mode of some compounds is in the tyrosinase binding pocket surrounding the copper in the active site. The correlation between the docking results with IC₅₀ values showed that the binding mode prediction of the test compounds would also be convincing. This comprehensive study allows for a possible mechanism for the antityrosinase activity of the sulfonamide chalcones. These sulfonamide chalcones bind to copper atoms of tyrosinase which responsible for the catalytic activity of tyrosinase. These compounds may be used as a lead for rational drug designing for the multi-functional tyrosinase inhibitor.

Keywords: Binding mode; molecular docking; sulfonamide chalcones; tyrosinase inhibitor

ABSTRAK

Dalam kajian ini, satu siri terbitan sulfonamida kalkon disintesis dan struktur kimianya disahkan oleh pencirian spektrum. Sebatian yang disintesis dinilai untuk aktiviti penghambatan tirosinasenya bersama dengan kajian mengedok molekul. Hasil perencatan tirosinase menunjukkan bahawa sebatian 5b, 5c, 5f, 5g dan 5h menunjukkan aktiviti penghambatan tirosinase yang signifikan dan setanding dengan ubat piawai (asid kojik). Sebatian 5c menunjukkan perencatan tirosinase yang paling kuat antara sebatian yang disintesis dengan IC₅₀ = 0.43 ± 0.07 mM, L-DOPA sebagai substrat dan lebih baik daripada asid kojik piawai (IC₅₀ = 0.60 ± 0.20 mM). Kajian mengedok molekul menunjukkan bahawa kaedah pengikatan sebilangan sebatian terdapat di dalam poket pengikat tirosinase yang mengelilingi tembaga di tapak aktif. Hubungan antara hasil dok dengan nilai IC₅₀ menunjukkan bahawa ramalan mod pengikat sebatian ujian juga akan meyakinkan. Kajian komprehensif ini memungkinkan adanya mekanisme untuk aktiviti anti-tirosinase sulfonamida kalkon. Kalkon sulfonamida ini mengikat atom tembaga tirosinase yang bertanggungjawab untuk aktiviti pemangkin tirosinase. Sebatian ini boleh digunakan sebagai petunjuk untuk mereka bentuk ubat yang rasional untuk perencat tirosinase pelbagai fungsi.

Kata kunci: Dok molekul; mod pengikat; perencat tirosinase; sulfonamida kalkon

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*Corresponding author; email: suchada.c@psu.ac.th