Design, synthesis, in vitro and in silico studies of naproxen derivatives as dual lipoxygenase and α-glucosidase inhibitors

• DOI: 10.1016/j.jscs.2022.101468
• Publication Date: 2022-04-01T17:43:22Z
• Authors: Asma Sardar; Obaid-ur-Rahman Abid; Saima Daud; M. Fakhar-e-Alam; Muhammad Hussnain...; Muhammad Ashraf; Wardah Shahid; Syeda Abida Ejaz; M. Atif; Shafiq Ahmad; Sulman Shafeeq; Muhammad Afzal
• Keywords: IC50

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