Abstract
Twenty novel chromene derivatives carrying different sulfonamide moieties (3–22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8–108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5–8, 11–14, and 16–18) on the aromatase activity was tested. Most of the selected compounds showed significant inhibitory effect on the aromatase activity, with compound 18 showing IC50 = 4.66 μM. Furthermore, apoptosis studies were conducted on two of the most potent compounds (8 & 16) to estimate the proapoptotic potential of our compounds. Both induced the levels of active caspase 3, caspase 8 and caspase 9. Moreover, they surprisingly boosted the Bax/Bcl2 ratio 5936 & 33,000 folds, respectively compared to the control. Moreover, they showed mild cytotoxic effect (IC50 = 183.8 μM & 172.04 μM, respectively) in normal breast cells 184A1. Finally, a molecular docking study was performed to investigate the probable interaction with the aromatase enzyme.
Twenty novel chromene derivatives carrying biologically active sulfonamide scaffold (3–22) were designed and synthesized ➨ Antiproliferative activity against T47D cell line ➨ Aromatase inhibitory activity ➨ Induction of both extrinsic and intrinsic pathways ➨ Cytotoxicity study on normal breast cells ➨ Cell cycle arrest at G2/M phase. [Display omitted]
•Twenty novel chromene derivatives carrying different sulfonamide scaffold were designed and synthesized.•Anti-proliferative activity was in vitro evaluated against T47D cells.•Aromatase inhibitory activity was evaluated for the most potent eleven compounds.