Multitarget Anticancer and Anti-Inflammatory Properties of a Novel Artesunate-Indole Hybrid: Synthesis and Functional Evaluation

An amide-bridged artesunate-indole hybrid molecule (TRY-ART) was investigated for its anticancer and anti-inflammatory activities. Cytotoxicity studies revealed that TRY-ART exhibited significant cytotoxicity against Caco-2, LNCaP, HepG2, Ishikawa, and A549 cancer cell lines, with EC50 values of 120.2 +/- 1.14, 79 +/- 0.54, 137.9 +/- 0.78, 94 +/- 2.37, and 183 +/- 1.65 mu M, respectively. Apoptosis analysis demonstrated that TRY-ART significantly induced apoptotic events in all tested cancer cell lines. It revealed its pro-apoptotic potential by upregulating the expression levels of pro-apoptotic genes (BAX, CASP3, CASP8, CASP9, and P53) and downregulating the anti-apoptotic gene BCL2. Colony-formation assays showed a reduction in colony formation capacity, and wound-healing assays indicated its efficacy against cell migration. qRT-PCR analysis revealed strong anti-migration effects by downregulating migration-related genes (MMP2 and MMP9) and upregulating their inhibitors (TIMP1 and TIMP2). Furthermore, anti-inflammatory evaluation by the Griess method in Lipopolysaccharide (LPS)-induced RAW264.7 macrophages revealed that TRY-ART suppressed nitric oxide production by 35% and significantly downregulated pro-inflammatory genes (Cox-2, Inos, Tnf-alpha, and Il6) while upregulating the anti-inflammatory gene Il10. In conclusion, the newly synthesized amide-bridged artesunate-indole hybrid molecule, TRY-ART, exhibits promising anticancer and anti-inflammatory properties.