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

Research output: Contribution to journalArticle

3 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 languageEnglish
Pages (from-to)4375-4383
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number16
DOIs
Publication statusPublished - 2017

Fingerprint

Narcotic Antagonists
Derivatives
Antitrichomonal Agents
Morphinans
Bearings (structural)
Trichomonas vaginalis
Naltrexone
Metronidazole
Opioid Receptors
Structure-Activity Relationship
Skeleton
Inhibitory Concentration 50
Pharmaceutical Preparations
7-benzylidenenaltrexone

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

Cite this

Kutsumura, N., Koyama, Y., Nagumo, Y., Nakajima, R., Miyata, Y., Yamamoto, N., ... Nagase, H. (2017). Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives. Bioorganic and Medicinal Chemistry, 25(16), 4375-4383. https://doi.org/10.1016/j.bmc.2017.06.026

Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives. / Kutsumura, Noriki; Koyama, Yasuaki; Nagumo, Yasuyuki; Nakajima, Ryo; Miyata, Yoshiyuki; Yamamoto, Naoshi; Saitoh, Tsuyoshi; Yoshida, Naoko; Iwata, Satoshi; Nagase, Hiroshi.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 16, 2017, p. 4375-4383.

Research output: Contribution to journalArticle

Kutsumura, N, Koyama, Y, Nagumo, Y, Nakajima, R, Miyata, Y, Yamamoto, N, Saitoh, T, Yoshida, N, Iwata, S & Nagase, H 2017, 'Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives', Bioorganic and Medicinal Chemistry, vol. 25, no. 16, pp. 4375-4383. https://doi.org/10.1016/j.bmc.2017.06.026
Kutsumura, Noriki ; Koyama, Yasuaki ; Nagumo, Yasuyuki ; Nakajima, Ryo ; Miyata, Yoshiyuki ; Yamamoto, Naoshi ; Saitoh, Tsuyoshi ; Yoshida, Naoko ; Iwata, Satoshi ; Nagase, Hiroshi. / Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 16. pp. 4375-4383.
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