Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B

Zenyu Shiokawa, Emi Kashiwabara, Daisuke Yoshidome, Koichi Fukase, Shinsuke Inuki, Yukari Fujimoto

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.

Original languageEnglish
Pages (from-to)2682-2689
Number of pages8
JournalChemMedChem
Volume11
Issue number24
DOIs
Publication statusPublished - 2016 Dec 16

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Alkaloids
Scaffolds
Thioamides
Derivatives
Immune system
longamide B
pyrrolopiperazinone
Tumors
Immune System
Neoplasms
Cells

Keywords

  • docking models
  • hanishin
  • indoleamine 2,3-dioxygenase 1
  • longamide B
  • piperazinones

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B. / Shiokawa, Zenyu; Kashiwabara, Emi; Yoshidome, Daisuke; Fukase, Koichi; Inuki, Shinsuke; Fujimoto, Yukari.

In: ChemMedChem, Vol. 11, No. 24, 16.12.2016, p. 2682-2689.

Research output: Contribution to journalArticle

Shiokawa, Zenyu ; Kashiwabara, Emi ; Yoshidome, Daisuke ; Fukase, Koichi ; Inuki, Shinsuke ; Fujimoto, Yukari. / Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B. In: ChemMedChem. 2016 ; Vol. 11, No. 24. pp. 2682-2689.
@article{3eb942ab3a934a6a8e83adbc4de4fcdc,
title = "Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B",
abstract = "Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.",
keywords = "docking models, hanishin, indoleamine 2,3-dioxygenase 1, longamide B, piperazinones",
author = "Zenyu Shiokawa and Emi Kashiwabara and Daisuke Yoshidome and Koichi Fukase and Shinsuke Inuki and Yukari Fujimoto",
year = "2016",
month = "12",
day = "16",
doi = "10.1002/cmdc.201600446",
language = "English",
volume = "11",
pages = "2682--2689",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "John Wiley and Sons Ltd",
number = "24",

}

TY - JOUR

T1 - Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B

AU - Shiokawa, Zenyu

AU - Kashiwabara, Emi

AU - Yoshidome, Daisuke

AU - Fukase, Koichi

AU - Inuki, Shinsuke

AU - Fujimoto, Yukari

PY - 2016/12/16

Y1 - 2016/12/16

N2 - Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.

AB - Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.

KW - docking models

KW - hanishin

KW - indoleamine 2,3-dioxygenase 1

KW - longamide B

KW - piperazinones

UR - http://www.scopus.com/inward/record.url?scp=85006357076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006357076&partnerID=8YFLogxK

U2 - 10.1002/cmdc.201600446

DO - 10.1002/cmdc.201600446

M3 - Article

C2 - 27863031

AN - SCOPUS:85006357076

VL - 11

SP - 2682

EP - 2689

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 24

ER -