ArticleAntimicrobial agents and chemotherapy2016
Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Discovery of a Baloxavir-Inspired Endonuclease Inhibitor That Prevents Herpes Simplex Virus 1 Replication in Cell Culture and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Harmol used for the treatment of herpes simplex virus induced keratitis.Virology journal · 2024Article
- In vitro evaluation of tropolone absorption, metabolism, and clearance.Antiviral research · 2023Article
- Antiviral activity of amide-appended α-hydroxytropolones against herpes simplex virus-1 and -2.RSC advances · 2023Article
- A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV.Cureus · 2023Review
- Synthetic derivatives of the antifungal drug ciclopirox are active against herpes simplex virus 2.European journal of medicinal chemistry · 2022Article
- Review
- Article
- Synthesis of Polyoxygenated Tropolones and their Antiviral Activity against Hepatitis B Virus and Herpes Simplex Virus-1.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Effects of Troponoids on Mitochondrial Function and Cytotoxicity.Antimicrobial agents and chemotherapy · 2022Article
- Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2.PLoS computational biology · 2021Article
- Amide-containing α-hydroxytropolones as inhibitors of hepatitis B virus replication.Antiviral research · 2020Article
- Anti-herpetic Activity ofFrontiers in microbiology · 2020Article
- Importance of lipophilicity for potent anti-herpes simplex virus-1 activity of α-hydroxytropolones.MedChemComm · 2019Article
- Divergent synthesis of a thiolate-based α-hydroxytropolone library with a dynamic bioactivity profile.RSC advances · 2019Article
- Article
- The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression.Journal of virology · 2018Article
- Sensitivity of the C-Terminal Nuclease Domain of Kaposi's Sarcoma-Associated Herpesvirus ORF29 to Two Classes of Active-Site Ligands.Antimicrobial agents and chemotherapy · 2018Article
- Amidation Strategy for Final-Step α-Hydroxytropolone Diversification.Tetrahedron letters · 2018Article
- Fluorous-Phase Approach to α-Hydroxytropolone Synthesis.The Journal of organic chemistry · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as β-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the α-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 μM, and 10 compounds inhibited HSV-1 and HSV-2 at 5 μM, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC50) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50] of 50 to >100 μM). Therapeutic indexes ranged from >170 to >1,200. These data indicate that troponoids and specifically α-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants.
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Registered trials
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