Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives
Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives
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δ 阿片受体拮抗剂、7-亚苄基纳曲酮衍生物的抗毛滴虫活性
DOI：
10.1016/j.bmc.2017.06.026
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发表时间：
2017
影响因子：
3.5
通讯作者：
Nagase Hiroshi
中科院分区：
文献类型：
--
作者：
Kutsumura Noriki;Koyama Yasuaki;Nagumo Yasuyuki;Nakajima Ryo;Miyata Yoshiyuki;Yamamoto Naoshi;Saitoh Tsuyoshi;Yoshida Naoko;Iwata Satoshi;Nagase Hiroshi
从纳曲酮（1）合成了7-亚苄基纳曲酮（BNTX）衍生物2a-v、3a-c、13 a-c和14 a，并评价了其抗毛虫活性。构效关系研究发现，4-碘-BNTX（2 g）显示出最高的活性（IC 50 = 10.5 µM），对阿片受体的亲和力对抗阴道毛滴虫的抗滴虫活性不太重要。带有迈克尔受体双键和酚羟基的吗啡喃骨架将是开发抗滴虫剂的特定模板。此外，BNTX衍生物的抗滴虫活性的机制可能不同于标准药物甲硝唑。
The 7-benzylidenenaltrexone (BNTX) derivatives2a–v,3a–c,13a–c, and14awere 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.