Thiosemicarbazide binds with the dicopper center in the competitive inhibition of mushroom tyrosinase enzyme: Synthesis and molecular modeling of theophylline analogues

Ahmed Bari; Usman Ghani; Saeed Ali Syed; Riazullah

doi:10.1016/j.bmcl.2021.127826

Thiosemicarbazide binds with the dicopper center in the competitive inhibition of mushroom tyrosinase enzyme: Synthesis and molecular modeling of theophylline analogues

Bioorg Med Chem Lett. 2021 Mar 15:36:127826. doi: 10.1016/j.bmcl.2021.127826. Epub 2021 Jan 26.

Authors

Ahmed Bari¹, Usman Ghani², Saeed Ali Syed³, Riazullah⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia; Research Center, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia. Electronic address: abari@ksu.edu.sa.
² Clinical Biochemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia; Research Center, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia.
⁴ Medicinal Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia.

PMID: 33513384
DOI: 10.1016/j.bmcl.2021.127826

Abstract

Theophylline is long known for its anti-ageing and anti-oxidative properties. Moreover, Tyrosinase is a crucial enzyme that regulates the melanin synthetic pathway, which is involved in various physiological metabolic processes including aging. The current paper describes the synthesis of various heterocyclic systems coupled with theophylline moiety along with their tyrosinase inhibition activity in view to identify the potent nucleus. Around 19 compounds were synthesized and screened for enzyme inhibition. Based on the current study, it is suggested that compound 18 having thiosemicarbazide has strong enzyme inhibition potential. The enzyme kinetics and docking studies provide important insights into how the compound interacts with the mushroom tyrosinase active site. The work will provide clue to developing new, potent tyrosinase inhibitors for drug development.

Keywords: Dermatological; Inhibition; Purine; Theophylline; Tyrosinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agaricales / enzymology
Binding Sites
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Copper / chemistry
Copper / pharmacology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Models, Molecular
Molecular Structure
Monophenol Monooxygenase / antagonists & inhibitors*
Monophenol Monooxygenase / metabolism
Semicarbazides / chemistry
Semicarbazides / pharmacology*
Structure-Activity Relationship
Theophylline / chemistry
Theophylline / pharmacology*

Substances

Coordination Complexes
Enzyme Inhibitors
Semicarbazides
thiosemicarbazide
Copper
Theophylline
Monophenol Monooxygenase