δ阿片受体拮抗剂7-亚苄基纳曲酮衍生物的抗滴虫活性

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

作者信息

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

机构信息

International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.

出版信息

Bioorg Med Chem. 2017 Aug 15;25(16):4375-4383. doi: 10.1016/j.bmc.2017.06.026. Epub 2017 Jun 15.

DOI:10.1016/j.bmc.2017.06.026

PMID:28662966

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=10.5µM) 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.

摘要

由纳曲酮（1）合成了7-亚苄基纳曲酮（BNTX）衍生物2a-v、3a-c、13a-c和14a，并对其抗滴虫活性进行了评估。构效关系研究发现，4-碘-BNTX（2g）表现出最高活性（IC = 10.5µM），且对阿片受体的亲和力对于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药物的特定模板。此外，BNTX衍生物的抗滴虫活性机制可能与标准药物甲硝唑不同。