Spectrofluorimetric and Computational Investigation of New Phthalimide Derivatives towards Human Neutrophil Elastase Inhibition and Antiproliferative Activity.

Herein, nine phthalimide-based thiazoles ( 4a - 4i ) were synthesized and investigated as new human neutrophil elastase (HNE) inhibitors using spectrofluorimetric and computational methods. The most active compounds containing 4-trifluoromethyl ( 4c ), 4-naphthyl ( 4e ) and 2,4,6-trichloro ( 4h ) substituents in the phenyl ring exhibited high HNE inhibitory activity with IC 50 values of 12.98-16.62 µM. Additionally, compound 4c exhibited mixed mechanism of action. Computational investigation provided a consistent picture of the ligand-receptor pattern of inter-actions, common for the whole considered group of compounds. Moreover, compounds 4b , 4c , 4d and 4f showed high antiproliferative activity against human cancer cells lines MV4-11, and A549 with IC 50 values of 8.21 to 25.57 µM. Additionally, compound 4g showed high activity against MDA-MB-231 and UMUC-3 with IC 50 values of 9.66 and 19.81 µM, respectively. Spectrophotometric analysis showed that the most active compound 4c demonstrated high stability under physiological conditions.