Artemisinin-isatin hybrids tethered via ethylene linker and their anti-lung cancer activity.

The synthesized 11 artemisinin-isatin hybrids 5a-c and 6a-h tethered via ethylene linker were assessed for their in vitro antiproliferative activity against A549 and H1299 nonsmall-cell lung cancer cell lines as well as their cytotoxicity towards BEAS-2B human normal lung epithelial cells. The preliminary results showed that hybrids 5a-c and 6a-h did not show any cytotoxicity (IC 50 : >100 µM) on BEAS-2B cells, and also possessed potential activity (IC 50 : 6.99-76.49 µM) against A549 and H1299 lung cancer cell lines. The representative hybrid 6c (IC 50 : 6.99 and 7.57 µM) was far more potent than artemisinin (IC 50 : >100 µM) and dihydroartemisinin (IC 50 : >100 µM), and was slightly less active than doxorubicin (IC 50 : 4.14 and 2.77 µM). Moreover, hybrid 6c also exhibited an excellent safety profile and good selectivity with SI values of >13.21. Therefore, hybrid 6c could serve as a promising candidate for further in vivo evaluations.