Synthesis, in vitro and in vivo evaluation of 2-aryl-4H-chromene and 3-aryl-1H-benzo[f]chromene derivatives as novel α-glucosidase inhibitors

Alexander A Spasov; Denis A Babkov; Dmitry V Osipov; Vladlen G Klochkov; Diana R Prilepskaya; Maxim R Demidov; Vitaly A Osyanin; Yuri N Klimochkin

doi:10.1016/j.bmcl.2018.10.018

Synthesis, in vitro and in vivo evaluation of 2-aryl-4H-chromene and 3-aryl-1H-benzo[f]chromene derivatives as novel α-glucosidase inhibitors

Bioorg Med Chem Lett. 2019 Jan 1;29(1):119-123. doi: 10.1016/j.bmcl.2018.10.018. Epub 2018 Oct 12.

Authors

Alexander A Spasov¹, Denis A Babkov², Dmitry V Osipov³, Vladlen G Klochkov¹, Diana R Prilepskaya⁴, Maxim R Demidov³, Vitaly A Osyanin³, Yuri N Klimochkin³

Affiliations

¹ Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshikh Bortsov Sq. 1, Volgograd 400131, Russia.
² Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshikh Bortsov Sq. 1, Volgograd 400131, Russia; Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya St. 39, Volgograd 400087, Russia. Electronic address: [email protected].
³ Department of Organic Chemistry, Samara State Technical University, Molodogvardeiskaya St. 244, Samara 443100, Russia.
⁴ Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya St. 39, Volgograd 400087, Russia.

PMID: 30340897
DOI: 10.1016/j.bmcl.2018.10.018

Abstract

Herein we report a study of novel arylchromene derivatives as analogs of naturally occurring flavonoids with prominent α-glucosidase inhibitory properties. Novel inhibitors were identified via simple stepwise in silico screening, efficient synthesis, and biological evaluation. It is shown that 2-aryl-4H-chromene core retains pharmacophore properties while being readily available synthetically. A lead compound identified through screening inhibits yeast α-glucosidase with IC₅₀ of 62.26 µM and prevents postprandial hyperglycemia in rats at 2.2 mg/kg dose.

Keywords: Chromene; Diabetes mellitus; Flavonoids; α-Glucosidase.

Publication types

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

MeSH terms

Administration, Oral
Animals
Benzopyrans / administration & dosage
Benzopyrans / chemistry
Benzopyrans / pharmacology*
Dose-Response Relationship, Drug
Glycoside Hydrolase Inhibitors / administration & dosage
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Male
Models, Molecular
Molecular Structure
Rats
Rats, Wistar
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / enzymology
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Benzopyrans
Glycoside Hydrolase Inhibitors
alpha-Glucosidases