Divergent Synthesis of a Thiolate-based α-hydroxytropolone Library with a Dynamic Bioactivity Profile

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2020 Oct 12

PMID 33042521

Citations 8

Authors

Nana B Agyemang

Cassandra R Kukla

Tiffany C Edwards

Qilan Li

Madison K Langen

Alexandra Schaal

Abaigeal D Franson

Andreu Gazquez Casals

Katherine A Donald

Alice J Yu

Maureen J Donlin

Lynda A Morrison

John E Tavis

Ryan P Murelli

Affiliations

Soon will be listed here.

Abstract

Here we describe a rapid and divergent synthetic route toward structurally novel αHTs functionalized with either one or two thioether or sulfonyl appendages. Evaluation of this library against hepatitis B and herpes simplex virus, as well as the pathogenic fungus , and a human hepatoblastoma (HepDES19) revealed complementary biological profiles and new lead compounds with sub-micromolar activity against each pathogen.

Citing Articles

In vitro evaluation of tropolone absorption, metabolism, and clearance.

Woodson M, Mottaleb M, Murelli R, Tavis J Antiviral Res. 2023; 220:105762.

PMID: 37996012 PMC: 10843707. DOI: 10.1016/j.antiviral.2023.105762.

Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.

Moianos D, Prifti G, Makri M, Zoidis G Pharmaceuticals (Basel). 2023; 16(6).

PMID: 37375848 PMC: 10304105. DOI: 10.3390/ph16060901.

Metal coordinating inhibitors of Rift Valley fever virus replication.

Geerling E, Murphy V, Mai M, Stone E, Gazquez Casals A, Hassert M PLoS One. 2022; 17(9):e0274266.

PMID: 36112605 PMC: 9481026. DOI: 10.1371/journal.pone.0274266.

Synthesis of α-Tropolones through Autoxidation of Dioxole-Fused Cycloheptatrienes.

Berkowitz A, Murelli R J Org Chem. 2022; 87(7):4499-4507.

PMID: 35007070 PMC: 9002940. DOI: 10.1021/acs.joc.1c02713.

Synthesis of Polyoxygenated Tropolones and their Antiviral Activity against Hepatitis B Virus and Herpes Simplex Virus-1.

Schiavone D, Kapkayeva D, Li Q, Woodson M, Gazquez Casals A, Morrison L Chemistry. 2022; 28(10):e202104112.

PMID: 34984767 PMC: 8858858. DOI: 10.1002/chem.202104112.

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