Khan, SirajBugday, NesrinYasar, SeymaRehman, Asim Ur.Ul Haq, IhsanYasar, Sedat2024-08-042024-08-0420230022-328X1872-8561https://doi.org/10.1016/j.jorganchem.2023.122794https://hdl.handle.net/11616/101431A series of 8-(hetero)aryl caffeine was synthesized by the C -H bond activation reaction using Pd-NHCs complexes as a catalyst. 8-(hetero)aryl caffeine derivatives were screened for their antioxidant, antimicro-bial, and enzyme inhibitory activities and in-silico studies. The 4a, 4b, 4e, 4f, 4 g, 4i, and 4n showed sig-nificant total antioxidant capacity (TAC) of 64.03, 50.87, 70.02, 98.14, 71.81, 45.48, and 44.28 & mu;g AAE/mg, respectively. The 4a, 4b, 4d, 4e, 6 h, 4i, 4j, 4k, and 4l were found active against Staphylococcus aureus at a minimum inhibitory concentration of 25, 12.5, 12.5, 12.5, 12.5, 6.25, 6.25, 6.25, and 6.25 & mu;g/ml, respec-tively. Some derivatives displayed activity against Escherichia coli, Bacillus subtilus, Klebsiella pneumonae, and Pseudomonas aeruginosa.A good activity was exhibited against Alternaria solani among five fungal strains. All the com-pounds (4a-4n) showed excellent protein kinase inhibitory activity except 4e, 4 g, and 4n. Addition-ally, 8-(hetero)aryl caffeine derivatives showed & alpha;-amylase inhibition potential (IC50 = 1.49 & PLUSMN; 0.317 to 7.44 & PLUSMN; 0.156 & mu;g/ml) compared to standard acarbose (IC50 = 4.34 & PLUSMN; 0.333 & mu;g/ml). The 4b, 4d, 4j, 4 m, and 4n compounds displayed good & alpha;-glucosidase inhibitory potential. Molecular modeling was done for protein kinase, & alpha;-amylase, and & alpha;-glucosidase. The results of these activities proved the caffeine deriva-tives to be bioactive.& COPY; 2023 Elsevier B.V. All rights reserved.eninfo:eu-repo/semantics/closedAccess8-(hetero)aryl xanthinesC -H bond activationBiological activitiesMolecular dockingStructure activity relationshipArticle99710.1016/j.jorganchem.2023.1227942-s2.0-85163173744Q3WOS:001030784000001Q2