Exploring ibuprofen derivatives as α‐glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies. Issue 8 (9th May 2022)

• Record Type: Journal Article
• Authors: Daud, Saima; Abid, Obaid‐ur‐Rahman; Sardar, Asma; Abdullah, Shawana; Shahid, Wardah; Ashraf, Muhammad; Ejaz, Syeda Abida; Saeed, Amna; Shah, Basit Ali; Niaz, Basit
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 8(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-09
• Subjects: 15‐LOX inhibition -- α‐glucosidase inhibition -- azole derivatives -- ibuprofen -- molecular docking; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202200013
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: This study reports the synthesis of a series of ibuprofen derivatives, including thiosemicarbazides 4a–f, 1, 3, 4‐oxadiazoles 5a–f, 1, 3, 4‐thiadiazoles 6a–f, 1, 2, 4‐triazoles 7a–f, and their S‐alkylated derivatives 8a–d . All of the newly synthesized derivatives were analyzed using 1 H NMR, 13 C NMR spectroscopy, and high‐resolution mass spectra (electron ionization) spectrometry. These synthetic molecules were examined for their in vitro baking yeast α‐glucosidase and soybean 15‐lipoxygenase (15‐LOX) inhibition and cell viability studies. The results revealed that the compounds N ‐(3, 4‐dichlorophenyl)−5‐[1‐(4‐isobutylphenyl)ethyl]‐1, 3, 4‐oxadiazol‐2‐amine 5f (IC50 3.05 ± 1.23 µM) and N ‐(3‐fluorophenyl)‐5‐[1‐(4‐isobutylphenyl)ethyl]‐1, 3, 4‐oxadiazol‐2‐amine 5b (IC50 3.12 ± 1.21 µM) were the most potent with respect to the α‐glucosidase enzyme while in case of 15‐LOX, the compound 4‐(2, 4‐dichlorophenyl)‐1‐[2‐(4‐isobutylphenyl)propanoyl]thiosemicarbazide 4e showed potent inhibition with an IC50 value of 55.41 ± 0.41 µM. All these compounds were found least toxic by displaying a blood mononuclear cell viability value of 69.2%–97.8% by the MTT assay compared to the standards when assayed at 0.25 mM concentration. Molecular docking analyses were conducted to evaluate the inhibition profiles of these derivatives against the said enzymes and the data supported the in vitro profiles. Abstract : A series of ibuprofen derivatives, including thiosemicarbazides 4a–f, 1, 3, 4‐oxadiazoles 5a–f, 1, 3, 4‐thiadiazoles 6a–f, 1, 2, 4‐triazoles 7a–f, and their S‐alkylated derivatives 8a–d, were synthesized and examined for their in vitro inhibitory effects on α‐glucosidase and 15‐lipoxygenase. The strongest inhibitory compounds (5f, 5b, and 4e ) were also found to be the least cytotoxic. Molecular docking analyses were conducted to evaluate their inhibition profiles.