Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives

Noriki Kutsumura; Yasuaki Koyama; Yasuyuki Nagumo; Ryo Nakajima; Yoshiyuki Miyata; Naoshi Yamamoto; Tsuyoshi Saitoh; Naoko Yoshida; Satoshi Iwata; Hiroshi Nagase

doi:10.1016/j.bmc.2017.06.026

Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives

Noriki Kutsumura, Yasuaki Koyama, Yasuyuki Nagumo, Ryo Nakajima, Yoshiyuki Miyata, Naoshi Yamamoto, Tsuyoshi Saitoh, Naoko Yoshida, Satoshi Iwata, Hiroshi Nagase

Department of Infectious Diseases

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

The 7-benzylidenenaltrexone (BNTX) derivatives 2a–v, 3a–c, 13a–c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC₅₀ = 10.5 µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.

Original language	English
Pages (from-to)	4375-4383
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2017.06.026
Publication status	Published - 2017

Keywords

Antitrichomonal activity
BNTX
Morphinan
Opioid receptor
Trichomonas

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2017.06.026

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title = "Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives",

abstract = "The 7-benzylidenenaltrexone (BNTX) derivatives 2a–v, 3a–c, 13a–c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50 = 10.5 µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.",

keywords = "Antitrichomonal activity, BNTX, Morphinan, Opioid receptor, Trichomonas",

author = "Noriki Kutsumura and Yasuaki Koyama and Yasuyuki Nagumo and Ryo Nakajima and Yoshiyuki Miyata and Naoshi Yamamoto and Tsuyoshi Saitoh and Naoko Yoshida and Satoshi Iwata and Hiroshi Nagase",

note = "Funding Information: This work was supported by JSPS KAKENHI (Grant-in-Aid for Young Scientists (B)) Grant Number 15K16553 (N.K.), 17K13259 (N.K.), and TORAY Industries, Inc. We thank Dr. S. Hirayama and Dr. H. Fujii (Kitasato University) for supporting the study on opioid receptor binding. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.bmc.2017.06.026",

language = "English",

volume = "25",

pages = "4375--4383",

journal = "Bioorganic and Medicinal Chemistry",

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T1 - Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives

AU - Kutsumura, Noriki

AU - Koyama, Yasuaki

AU - Nagumo, Yasuyuki

AU - Nakajima, Ryo

AU - Miyata, Yoshiyuki

AU - Yamamoto, Naoshi

AU - Saitoh, Tsuyoshi

AU - Yoshida, Naoko

AU - Iwata, Satoshi

AU - Nagase, Hiroshi

N1 - Funding Information: This work was supported by JSPS KAKENHI (Grant-in-Aid for Young Scientists (B)) Grant Number 15K16553 (N.K.), 17K13259 (N.K.), and TORAY Industries, Inc. We thank Dr. S. Hirayama and Dr. H. Fujii (Kitasato University) for supporting the study on opioid receptor binding. Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017

Y1 - 2017

N2 - The 7-benzylidenenaltrexone (BNTX) derivatives 2a–v, 3a–c, 13a–c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50 = 10.5 µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.

AB - The 7-benzylidenenaltrexone (BNTX) derivatives 2a–v, 3a–c, 13a–c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50 = 10.5 µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.

KW - Antitrichomonal activity

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KW - Opioid receptor

KW - Trichomonas

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Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives

Abstract

Keywords

ASJC Scopus subject areas

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