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Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38.

ABSTRACT: Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure-activity relationships of reported small-molecule thiazoloquinolinones and show that several 4-cyclohexylamino analogues have potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine analogues could be acylated and functionalized with alkyne and fluorescein groups. Fluorescein analogue 21 bound selectively to CD38 overexpressing cells, demonstrating the potential utility of thiazoloquinolinones as small-molecule conjugates for the delivery of therapeutic and imaging agents.

SUBMITTER: Scully SS

PROVIDER: S-EPMC5304304 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Thiazoloquinolinones with Linkers To Enable Targeting of CD38.

Scully Stephen S SS Minden Zachary J ZJ Mukerji Ratul R Andrianova Elizaveta E Kaberna James J Lentini Scott S Tassa Carlos C Wang Zhaolin Z Low Susan S McDonnell Kevin A KA

ACS medicinal chemistry letters 20161222 2

Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure-activity relationships of reported small-molecule thiazoloquinolinones and show that several 4-cyclohexylamino analogues have potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine analogues could be acylated and functionalized with alkyne and fluorescein groups. Fluorescein analogue <b>2 ...[more]

PMID: 28197311

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