Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation †

Hyun Su Kim; Hyejin Kong; Taewoo Kim; Changjin Lim; Seungbeom Lee; Seok Ho Kim; Young Ger Suh

doi:10.3390/md21050281

Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation †

Hyun Su Kim
, Hyejin Kong
, Taewoo Kim
, Changjin Lim
, Seungbeom Lee
, Seok Ho Kim
, Young Ger Suh^*

^*Corresponding author for this work

Department of Pharmacy

Research output: Contribution to journal › Journal article › peer-review

1 Scopus citations

Abstract

This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

Original language	English
Article number	281
Journal	Marine Drugs
Volume	21
Issue number	5
DOIs	https://doi.org/10.3390/md21050281
State	Published - 2023.05

Keywords

cathepsin D
izenamides
linear depsipeptides
marine cyanobacteria
statine

Quacquarelli Symonds(QS) Subject Topics

Pharmacy & Pharmacology

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10.3390/md21050281

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title = "Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation †",

abstract = "This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.",

keywords = "cathepsin D, izenamides, linear depsipeptides, marine cyanobacteria, statine",

author = "Kim, \{Hyun Su\} and Hyejin Kong and Taewoo Kim and Changjin Lim and Seungbeom Lee and Kim, \{Seok Ho\} and Suh, \{Young Ger\}",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = may,

doi = "10.3390/md21050281",

language = "English",

volume = "21",

journal = "Marine Drugs",

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TY - JOUR

T1 - Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition

T2 - Insights from Synthesis-Derived Elucidation †

AU - Kim, Hyun Su

AU - Kong, Hyejin

AU - Kim, Taewoo

AU - Lim, Changjin

AU - Lee, Seungbeom

AU - Kim, Seok Ho

AU - Suh, Young Ger

PY - 2023/5

Y1 - 2023/5

N2 - This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

AB - This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

KW - cathepsin D

KW - izenamides

KW - linear depsipeptides

KW - marine cyanobacteria

KW - statine

UR - https://www.scopus.com/pages/publications/85160307864

U2 - 10.3390/md21050281

DO - 10.3390/md21050281

M3 - Journal article

C2 - 37233475

AN - SCOPUS:85160307864

SN - 1660-3397

VL - 21

JO - Marine Drugs

JF - Marine Drugs

IS - 5

M1 - 281

ER -

Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation †

Abstract

Keywords

Quacquarelli Symonds(QS) Subject Topics

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