Synthesis and cytotoxic activity of novel dihydroartemisinin-nonsteroidal anti-inflammatory drug conjugates

In this study, a series of novel dihydroartemisinin-nonsteroidal anti-inflammatory drug conjugates was designed and synthesised. The cytotoxic effects of these compounds against human leukemic K562 and multidrug-resistant K562/ADR cell lines were evaluated using the CCK-8 assay <i>in vitro</i>. Most hybrids exhibited higher anticancer activities than dihydroartemisinin. Among them, compound <b>KL-7</b> demonstrated the highest potency, with IC₅₀ values of 0.11 ± 0.01 μM and 0.34 ± 0.02 μM against K562 and K562/ADR cells, respectively. Moreover, <b>KL-7</b> showed selectivity comparable to that of the positive drug etoposide. Further analysis revealed that <b>KL-7</b> significantly induced apoptosis in K562/ADR cells. The drug-likeness of <b>KL-7</b> was also predicted.