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The article discusses the synthesis and biological evaluation of biarylamide derivatives that are inhibitors of phagocytosis in macrophages. Topics include the immune cells macrophages which are important innate immune system, the phagocytosis process that involves a number of biomolecules such as cell surface receptors and cytoskeletal proteins and the use of potent small molecules against phagocytosis for exploring structure-activity relationship (SAR) of the biaryl amide compounds.

Abstract: 5,6,7,8-Tetrahydro-4H-cyclohepta[d]isoxazole derivatives were synthesized and evaluated as a novel class of inhibitors for α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis in a mouse melanoma B16F10 cell line. Compound 8e (IC50 =0.67μM), 8h (IC50 =1.01μM) and 9b (IC50 =0.99μM) exhibited a potent inhibitory activity approximately 85- to 126-fold greater than kojic acid, a well-known potent inhibitor. A biochemical study indicates that the activity of this series should be displayed via down-regulation of the expression of tyrosinase. [Copyright &y& Elsevier]

Abstract: Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immune response to microbial infections. To find small molecule regulators for the investigation of complicated phagocytic process, we screened our in-house chemical library and found chemicals which inhibit phagocytosis of zymosan by macrophages. A representative compound 5a reduced phagocytosis of zymosan in both peritoneal macrophages and RAW264.7 cells in a dose-dependent manner. Treatment of 5a led to downregulate the key regulators of phagocytosis, Rac1, Rac2 and Cdc42, and slightly reduced phosphorylation of Akt by zymosan. [Copyright &y& Elsevier]

Abstract: 1,3,4-Oxadiazole derivatives were found to enhance astrocyte differentiation in rat fetal neural stem cells (NSCs). Differentiation activity was assessed by immunocytochemistry and analysis of mRNA expression of astrocyte markers, GFAP and S100. Compounds 7 and 8 showed approximately a two-fold increase in astrocyte differentiation without engagement of neuronal differentiation and detectable cytotoxicity. [Copyright &y& Elsevier]