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3-Substituted Biquinolinium Inhibitors of AraC Family Transcriptional Activator VirF from S. flexneri Obtained Through In Situ Chemical Ionization of 3,4-Disubstituted Dihydroquinolines.

ABSTRACT: During a structure-activity relationship optimization campaign to develop an inhibitor of AraC family transcriptional activators, we discovered an unexpected transformation of a previously reported inhibitor that occurs under the assay conditions. Once placed in the assay media, the 3, 4-disubstituted dihydroquinoline core of the active analogue rapidly undergoes a decomposition reaction to a quaternary 3-substituted biquinolinium. Further examination established an SAR for this chemotype while also demonstrating its resilience to irreversible binding of biologically relevant nucleophiles.

SUBMITTER: Jain P

PROVIDER: S-EPMC4170738 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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3-Substituted Biquinolinium Inhibitors of AraC Family Transcriptional Activator VirF from <i>S. flexneri</i> Obtained Through In Situ Chemical Ionization of 3,4-Disubstituted Dihydroquinolines.

Jain Prashi P Li Jiaqin J Porubsky Patrick P Neuenswander Benjamin B Egan Susan M SM Aubé Jeffrey J Rogers Steven S

RSC advances 20140101 75

During a structure-activity relationship optimization campaign to develop an inhibitor of AraC family transcriptional activators, we discovered an unexpected transformation of a previously reported inhibitor that occurs under the assay conditions. Once placed in the assay media, the 3, 4-disubstituted dihydroquinoline core of the active analogue rapidly undergoes a decomposition reaction to a quaternary 3-substituted biquinolinium. Further examination established an SAR for this chemotype while ...[more]

PMID: 25258678

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