Advances in anti-Trichomonas vaginalis target and drug research

doi:10.12140/j.issn.1000-7423.2024.01.015

Abstract

Abstract:

Trichomonas vaginalis mainly invades the human genitourinary system and is a common non-viral sexually transmitted pathogen in clinics. Oral metronidazole is a widely used treatment, but the resistance of T. vaginalis to metronidazole has been spreading due to monotherapies in the past, so it is urgent to find alternative means. In this paper, the relavent research on anti-T. vaginalis targets and treatments in recent years were summarized and analyzed. The new advances were specifically introduced to provide a reference for future research and applications.

Key words: Trichomoniasis vaginalis, Target, Drug, Research progress

CLC Number:

R382.211

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.

Figures/Tables 1

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	[8-9]
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	[11]
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	[16]
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	[18,34]
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	[19]
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	[20-21] [23]
-	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	[24]
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	[27]
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	[28]
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	[29]
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）	[30]
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	[31]
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	[37]
-	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	[39]

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