中国寄生虫学与寄生虫病杂志 ›› 2024, Vol. 42 ›› Issue (1): 105-110.doi: 10.12140/j.issn.1000-7423.2024.01.015
收稿日期:
2023-11-22
修回日期:
2024-01-24
出版日期:
2024-02-28
发布日期:
2024-03-12
通讯作者:
周欣
作者简介:
周欣(1993—),女,本科,住院医师,从事妇产科疾病诊治。E-mail:17781759380@163.com
Received:
2023-11-22
Revised:
2024-01-24
Online:
2024-02-28
Published:
2024-03-12
Contact:
ZHUO Xin
摘要:
阴道毛滴虫主要侵犯人体泌尿生殖系统,是临床常见非病毒性传播病原。口服甲硝唑是目前普遍采用的治疗手段,但长期单一使用造成阴道毛滴虫对甲硝唑的耐药性不断增强,因此迫切需要寻找替代疗法。本文对近年来抗阴道毛滴虫靶点及药物的相关研究进行归纳分析,重点介绍取得的新进展,以期为后续研究和应用提供参考。
中图分类号:
周欣, 黄翠兰. 抗阴道毛滴虫靶点及药物研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(1): 105-110.
ZHUO Xin, HUANG Cuilan. Advances in anti-Trichomonas vaginalis target and drug research[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2024, 42(1): 105-110.
表1
抗阴道毛滴虫重要靶点及药物
靶标 | 候选药物 | 作用特点 | 文献 |
---|---|---|---|
20S蛋白酶体 | CP-17 | 低浓度优先抑制β5,高浓度同时抑制β5、β2。体外活性较甲硝唑强,细胞毒性较CPB低 | [ |
磷酸丙糖异构酶 | A4 | 与阴道毛滴虫磷酸丙糖异构酶结合,但不抑制其酶活性。有体外杀滴虫活性,无细胞毒性 | [ |
碳酸酐酶 | 乙酰唑胺 依索唑胺 | 取代水分子/氢氧根离子与锌离子结合,抑制碳酸酐酶活性,二者的抑制常数达到纳摩尔级 | [ |
金属肽酶TvMP50 | 铜-苯二酮 | 与TvMP50活性中心的组氨酸335相互作用,减少金属肽酶相关基因的表达;IC50达0.84 µmol/L | [ |
G6PD-6PGL | CNZ-3、 CNZ-17 | CNZ-3竞争性抑制,CNZ-177非竞争性抑制;IC50值分别为93.0 、356.0 μmol/L;CNZ-3不具备选择性,CNZ-17选择性较强 | [ |
黏附相关蛋白 | - | 黏附蛋白33、黏附蛋白65与人促凋亡蛋白BNIP3相互作用;肌动蛋白加帽蛋白亚基调控滴虫的细胞骨架,细胞骨架抑制剂和酪蛋白激酶-2抑制剂可抑制这种调节作用 | [ [ |
- | PH100 | 降低肽酶活性,诱导滋养体凋亡;IC50达14.8 µmol/L,MIC可达80 µmol/L,与甲硝唑有协同作用,细胞毒性低,无溶血作用 | [ |
金属肽酶TvMP50 | ATZ-1 ATZ-2 | ATZ-1、ATZ-2与TvMP50活性中心强相互作用,显著下调TvMP50的活性,同时降低TvMP50的基因表达。以剂量依赖性方式抑制阴道毛滴虫的生长,IC50分别为0.15 、0.18 μg/ml | [ |
嘌呤核苷磷酸化酶、乳酸脱氢酶等 | QDA-1 | 促进活性氧产生和脂质过氧化,IC50为113.8 μmol/L,160 μmol/L时完全抑制滋养体生长,有一定的细胞毒性 | [ |
金属肽酶 | PH152 | 作用于金属肽酶的铁离子,IC50为16.88 μmol/L,对人细胞无毒性 | [ |
丙酮酸铁氧还蛋白氧化还原酶 | Amixicile | 对9个分离株的MIC一致性较低,中位MIC值为6.25 μmol/L(1.56 μmol/L,12.5 μmol/L) | [ |
G6PD-6PGL | O2N-BZM7、 O2N-BZM9 | 二者均能改变G6PD-6PGL的三维结构,导致酶的活性丧失,且O2N-BZM9比O2N-BZM7更快形成酶-抑制剂复合物。IC50分别为22 、240 μmol/L | [ |
嘌呤核苷磷酸化酶 | 4-羟基查尔酮 | 作用于嘌呤核苷磷酸化酶的氨基酸残基,4-羟基查尔酮的IC50为27.5 μmol/L,对人红细胞无毒性 | [ |
- | SQ109 | SQ109能导致滋养体出现表面凸起增加,胞质内氢化小体肿胀等超微结构变化,IC50为3.15 μmol/L | [ |
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