Biological evaluation of selected 3,4‐dihydro‐2(1 H H )‐quinoxalinones and 3,4‐dihydro‐1,4‐benzoxazin‐2‐ones: Molecular docking study

摘要

Abstract In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4‐benzoxazin‐2‐ones. The results obtained showed that compounds 5 , 9–11 have good cytotoxic activity against HeLa cells where the lowest IC 50 value (10.46?±?0.82?μM/mL) was measured for compound 10 . Additionally, the most active compounds ( 5 , 9 – 11 ) showed much better selectivity for MRC‐5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α‐glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54?±?0.09 and 40.09?±?0.49?μM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB‐DNA complex through intercalation, suggesting good competition with EB ( K sv ?=?(3.1?±?0.2), (5.1?±?0.1), (5.6?±?0.2), and (6.3?±?0.2)?×?10 3 ?M ?1 ). A molecular docking study was also performed to better understand the binding modes and to conclude the structure–activity relationships of the synthesized compounds.