Antiviral Activity of 1,4-Disubstituted-1,2,3-Triazoles against HSV-1 in vitro

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 mM for 24 h. The 50% effective drug concentration (EC 50 ) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC 50 ) 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-phenylen ebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl))dibenzaldehyde) were the most promising, with an EC 50 of 16 and 21 mM and CC 50 of 285 and 2,593 mM, 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.

An Efficient Synthesis, Antimicrobial Evaluation and In Silico Studies of 1,2,3‐Triazolyl‐isoxazolyl‐ethanol Derivatives

“…The 1,2,3-triazole is one of the prominent scaffolds used for the development of the active compounds. [24][25][26][27] 1,2,3-Triazole-containing compounds received more attention due to their varied biological activities such as antifungal, [28][29][30][31][32][33][34] antimicrobial, [35,36] antivirals, [37,38] antimalarial, [39,40] anticancer [41][42][43] and anti-inflammatory activities. [44,45] The isoxazole containing natural and synthetic compounds reported for a wide range of biological activities such as antimicrobial, [46,47] antibacterial, [48][49][50] antifungal, [51,52] antitubercular, [16,[53][54][55] antiviral, [56,57] anticancer, [58][59][60] and anti-inflammatory.…”

Synthesis of New Imidazo[1,2‐a]pyridine Triazole Hybrid Molecules as Potential Apoptotic Antitumor Agents

“…Compared with other heterocyclic compounds, they are stated to be quite stable against metabolic degradation. [18,19] They exhibit many different therapeutic properties such as antimicrobial, [20] antibacterial, [21] antiviral, [22] anticholinesterase, [23] antioxidants, [24] antidiabetic, [25] anticancer, [26] and antiinflammatory. [27] In addition, 1,2,3-triazole hybrid pharmacophores are highly effective against drugsensitive, drug-resistant cancer cell lines [28][29][30] and they show anticancer effects through different pathways including inhibition of enzymes, PARP-1, tubulin, carbonic anhydrases (CA's), aromatase, indoleamine 2,3-dioxygenase 1 (IDO1), epidermal growth factor receptor (EGFR).…”

1,2,3-Triazole Containing Hybrids as Potential Pharmacological Agents: A Review

“…1,2,3-Triazole is a promising heterocyclic motif, its derivatives exhibit a wide variety of pharmacological properties, including antibacterial [10], antifungal [11,12], antimalarial [13], antileishmanial [14], antitubercular [15], antiviral [16], anticancer [17], antiepileptic [18], anti-inflammatory [19] and α-glycosidase inhibitor activities, etc. [20].…”