SAR optimization studies on modified salicylamides as a potential treatment for acute myeloid leukemia through inhibition of the CREB pathway [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 541 Physical chemistry
• Thông tin xuất bản: Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2019
• Mô tả vật lý: Size: p. 2307-2315 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261862
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 59 basic biological sciences; 3. 60 applied life sciences; 4. Acute myeloid leukemia; 5. Cbp; 6. Creb; 7. Salicylamide; 8. Small molecule

Tóm tắt

Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. In this paper, we describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.