Syntheses and Glycosidase Inhibitory Activities, and in Silico Docking Studies of Pericosine E Analogs Methoxy-Substituted at C6.


Journal

Marine drugs
ISSN: 1660-3397
Titre abrégé: Mar Drugs
Pays: Switzerland
ID NLM: 101213729

Informations de publication

Date de publication:
20 Apr 2020
Historique:
received: 15 02 2020
revised: 15 04 2020
accepted: 17 04 2020
entrez: 25 4 2020
pubmed: 25 4 2020
medline: 17 2 2021
Statut: epublish

Résumé

Inspired by the significant -glucosidase inhibitory activities of (+)- and (-)-pericosine E, we herein designed and synthesized 16 analogs of these marine natural products bearing a methoxy group instead of a chlorine atom at C6. Four of these compounds exhibited moderate -glucosidase inhibitory activities, which were weaker than those of the corresponding chlorine-containing species. The four compounds could be prepared by coupling reactions utilizing the (-)-pericosine B moiety. An additional in silico docking simulation suggested that the reason of reduced activity of the C6-methoxylated analogs might be an absence of hydrogen bonding between a methoxy group with the surrounding amino acid residues in the active site in -glucosidase.

Identifiants

pubmed: 32326065
pii: md18040221
doi: 10.3390/md18040221
pmc: PMC7230162
pii:
doi:

Substances chimiques

Glycoside Hydrolase Inhibitors 0
Ligands 0
pericosine E 0
Shikimic Acid 29MS2WI2NU
alpha-Glucosidases EC 3.2.1.20

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Yoshihide Usami (Y)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Megumi Higuchi (M)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Koji Mizuki (K)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Mizuki Yamamoto (M)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Mao Kanki (M)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Chika Nakasone (C)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Yuya Sugimoto (Y)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Makio Shibano (M)

Department of Natural Products Research, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Yoshihiro Uesawa (Y)

Department of Medical Molecular Informatics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.

Junko Nagai (J)

Department of Medical Molecular Informatics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.

Hiroki Yoneyama (H)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

Shinya Harusawa (S)

Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.

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Classifications MeSH