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 (IC 50  = 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.