Direct Synthesis of 2-Acyl Acridines Using Aldimines and Anthranils: Evaluation of Cytotoxicity and Anti-Inflammatory Activity

Rhodium (III)-catalyzed C−H aminations of aldimines with anthranils followed by intramolecular cyclization are described. These transformations facilitate the efficient generation of 2-acyl acridines, which are important motifs found in bioactive natural products and pharmaceuticals. All synthesized 2-acyl acridines were first screened for cytotoxic activity against human renal carcinoma cells (CAKI-1 and 786-O) and human breast carcinoma cells (MCF-7). Compound 3 z showed the most potent cytotoxic activity, which is stronger than that of doxorubicin against CAKI-1 and 786-O cells. In addition, compounds that exhibited potent cytotoxicities were selected for further in vitro anti-inflammatory activity testing using interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds (3 k, 3 n, 3 s and 3 x–3 z) were found to exhibit inhibitory activities that are about two- to three-times more potent than that of the anti-inflammatory drug dexamethasone.