Abstract
A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC50 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC50 36.53 ± 0.51 µM) and 4d (IC50 49.62 ± 0.12 µM) against standard drug baicalein (IC50 22.46 ± 1.32 µM) and quercetin (IC50 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC50 1.13 ± 0.62 µM −123.47 ± 0.37 µM. Among these compounds, 4e (IC50 1.13 ± 0.62 µM), 5b (IC50 1.19 ± 0.43 µM), 8c (IC50 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC50 4.86 ± 0.14 µM), and baicalein (IC50 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC50 1.0 ± 1.13 µM − 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC50 375.82 ± 1.76 µM), while compound 6c (IC50 1.0 ± 1.13 µM) and 7c (IC50 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.