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 (IC50: >100 mu M) on BEAS-2B cells, and also possessed potential activity (IC50: 6.99-76.49 mu M) against A549 and H1299 lung cancer cell lines. The representative hybrid 6c (IC50: 6.99 and 7.57 mu M) was far more potent than artemisinin (IC50: >100 mu M) and dihydroartemisinin (IC50: >100 mu M), and was slightly less active than doxorubicin (IC50: 4.14 and 2.77 mu M). 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.

Automated summary

In this study, eleven artemisinin-isatin hybrids tethered via ethylene linker were synthesized and evaluated for their antiproliferative activity against lung cancer cell lines and cytotoxicity towards normal lung epithelial cells. The results showed that these hybrids exhibited potential activity against the cancer cell lines while being non-toxic to normal cells. Moreover, one representative hybrid showed even better potency than traditional chemotherapy drugs and demonstrated excellent safety and selectivity.