Antiviral activity of 1,4-disubstituted-1,2,3-triazoles against HSV-1 in vitro.

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Antiviral Therapy Pub Date : 2020-01-01 DOI:10.3851/IMP3387
Daiane J Viegas, Verônica D da Silva, Camilla D Buarque, David C Bloom, Paula A Abreu
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引用次数: 6

Abstract

Background: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action.

Methods: Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 μM for 24 h. The 50% effective drug concentration (EC50) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC50) determined using CellTiter-Glo® solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain.

Results: Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC50 of 16 and 21 μM and CC50 of 285 and 2,593 μM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5.

Conclusions: Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.

1,4-二取代-1,2,3-三唑对HSV-1的体外抗病毒活性研究。
背景:单纯疱疹病毒1型(HSV-1)影响很大一部分成年人。抗hsv -1药物,如无环鸟苷,靶向胸苷激酶和病毒DNA聚合酶。然而,1型单纯疱疹病毒耐药性的出现提醒了开发具有其他治疗靶点的新抗病毒药物的紧迫性。因此,本研究评估了一系列1,4-二取代-1,2,3-三唑衍生物对HSV-1急性感染的作用,并为可能的作用机制提供了更深入的见解。方法:用HSV-1 17syn+感染人成纤维细胞(HFL-1),用三唑类化合物在50 μM下作用24 h,测定活性化合物的50%有效药物浓度(EC50)。用CellTiter-Glo®溶液测定50%细胞毒性浓度(CC50),在HFL-1中评估它们的细胞毒性。这些最有希望的化合物通过杀病毒活性、对病毒输出、DNA复制和转录的影响以及对无环韦耐药的HSV-1株的作用进行了评价。结果:化合物3 ((E)-4-甲基- n '-(2-(4-(苯氧甲基)- 1h -1,2,3-三唑基)苄基)苯磺酰肼)和4(2,2'-(4,4'-(1,3-苯双(氧))双(亚甲基))双(1h -1,2,3-三唑-4,1二基))二苯甲醛)是最有前途的化合物,EC50分别为16和21 μM, CC50分别为285和2,593 μM。化合物3能够抑制抗阿昔洛韦毒株的复制并干扰病毒的逸出。两种化合物均不影响病毒DNA复制,但显著抑制ICP0、ICP4和gC的表达。化合物4也影响UL30和ICP34.5的转录。结论:我们的研究结果表明,这些化合物具有与阿昔洛韦不同的作用机制,是有希望的抗病毒候选者,值得进一步研究。
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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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