Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Kutsumura, Noriki; Koyama, Yasuaki; Nagumo, Yasuyuki; Nakajima, Ryo; Miyata, Yoshiyuki; Yamamoto, Naoshi; Saitoh, Tsuyoshi; Yoshida, Naoko; Iwata, Satoshi; Nagase, Hiroshi
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 16(2017)
• Page Start: 4375
• Page End: 4383
• Publication Date: 2017-08-15
• Subjects: Antitrichomonal activity -- Opioid receptor -- BNTX -- Morphinan -- Trichomonas; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.06.026
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The 7-benzylidenenaltrexone (BNTX) derivatives2a–v, 3a–c, 13a–c, and14a 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.