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Importance of lipophilicity for potent anti-herpes simplex virus-1 activity of ?-hydroxytropolones.

ABSTRACT: We previously reported that troponoid compounds profoundly inhibit replication of herpes simplex virus (HSV)-1 and HSV-2 in cell culture, including acyclovir-resistant mutants. Synthesis of 26 alpha-hydroxylated tropolones (?HTs) led to a preliminary structure-activity relationship highlighting the potency of bi-phenyl side chains. Here, we explore the structure-activity relationship in more detail, with a focus on various biaryl and other lipophilic molecules. Along with our prior structure-function analysis, we present a refined structure-activity relationship that reveals the importance of the lipophilicity and nature of the side chain for potent anti-HSV-1 activity in cells. We expect this new information will help guide future optimization of ?HTs as HSV antivirals.

SUBMITTER: Berkowitz AJ

PROVIDER: S-EPMC6640544 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Importance of lipophilicity for potent anti-herpes simplex virus-1 activity of α-hydroxytropolones.

Berkowitz Alex J AJ Franson Abaigeal D AD Gazquez Cassals Andreu A Donald Katherine A KA Yu Alice J AJ Garimallaprabhakaran Aswin K AK Morrison Lynda A LA Murelli Ryan P RP

MedChemComm 20190530 7

We previously reported that troponoid compounds profoundly inhibit replication of herpes simplex virus (HSV)-1 and HSV-2 in cell culture, including acyclovir-resistant mutants. Synthesis of 26 alpha-hydroxylated tropolones (αHTs) led to a preliminary structure-activity relationship highlighting the potency of bi-phenyl side chains. Here, we explore the structure-activity relationship in more detail, with a focus on various biaryl and other lipophilic molecules. Along with our prior structure-fun ...[more]

PMID: 31391890

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