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ID: ALA3875186

Journal: Bioorg Med Chem Lett

Title: Design, synthesis, and characterization of rhein analogs as novel inhibitors of scavenger receptor A.

Authors: Zheng Y, Li X, Pagare PP, Yuan Y, Wang XY, Zhang Y.

Abstract: Scavenger receptor A (SRA) has been known as an immunosuppressive factor and therefore therapeutic inhibition of SRA may be potentially exploited for cancer immunotherapy. Our previously work suggested that rhein may act as an inhibitor of SRA in reversing immunosuppression of SRA during T cells activation. Herein, three deconstruction analogs of rhein, compound 1, 2, and 3, were further studied as inhibitors of SRA. These three compounds, particularly compound 1, also known as a natural product danthron, enhanced T cells activation, indicated by increased transcriptional activation of interleukin 2 (Il2) gene, production of IL-2 protein, and proliferation of T cells. Additionally, the interaction between these compounds and SRA was studied by molecular modeling. Compound 1 showed a favorable binding mode with the cysteine rich domain of SRA protein compared to compound 2 and 3. Collectively, those results would provide insight for future design and development of next generation rhein derivatives as SRA inhibitors.

CiteXplore: 27884693

DOI: 10.1016/j.bmcl.2016.11.029