Abstract
CCL2 overexpression is associated with macrophage recruitment during immune response and poor patient prognosis in various cancers, such as prostate, breast, pancreatic, and liver cancer. For developing CCL2 inhibitors, 1-aryloxymethyl-2,4,5-trifluorobenzene analogs were designed and synthesized by concise synthetic route including SN2 reaction, reduction, and oxime formation reaction. Furthermore, it was confirmed that they inhibited CCL2 production induced by 27-hydroxycholesterol through reverse transcription PCR in the human acute monocytic leukemia cell line (THP-1). Among them, N-((2-(2,4,5-trifluorobenzyloxy)naphthalene-1-yl)methyl)hydroxylamine (4) exhibited the highest CCL2 transcription inhibition activity.
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