Title

Development Of Flavonoid-Based Inverse Agonists Of The Key Signaling Receptor Us28 Of Human Cytomegalovirus

Abstract

A series of 31 chalcone- and flavonoid-based derivatives were synthesized in good overall yields and screened for their inverse agonist activity on the US28 receptor of human cytomegalovirus (HCMV). With one exception (e.g., 2-(5-bromo-2-methoxyphenyl)-3-hydroxy-4H-chromen-4-one), halogen-substituted flavonoids were typically more potent inverse agonists than their related hydro derivatives. While toxicity could be used to partially explain the inverse agonist activity of some members of the series, 5-(benzyloxy)-2-(5-bromo-2- methoxyphenyl)-4H-chromen-4-one (11b) acted on the US28 receptor as a nontoxic, inverse agonist. The full inverse agonism (efficacy, -89%) and potency (EC 50 = 3.5 μM) observed with flavonoid 11b is especially important as it provides both a new tool to study US28 signaling and a potential platform for the future development of HCMV-targeting drugs. © 2013 American Chemical Society.

Publication Date

6-27-2013

Publication Title

Journal of Medicinal Chemistry

Volume

56

Issue

12

Number of Pages

5019-5032

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jm4003457

Socpus ID

84879592007 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84879592007

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