RESUMO
Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study
Assuntos
Produtos Biológicos/análise , Espectrometria de Massas/métodos , Espectroscopia de Ressonância Magnética/métodos , Inibidores da Colinesterase/efeitos adversos , Acarbose/efeitos adversos , Amidas/agonistas , Antioxidantes/análiseRESUMO
Our purposes were to perform the pharmacological characterization of PGF(2alpha) receptor (prostanoid FP-receptor) involved in human umbilical vein contraction and confirm its expression in this tissue. Umbilical cords from healthy patients after full-term deliveries were employed. The vein was dissected out of cords and used for either isolated organ bath or reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. The natural prostanoid FP-receptor agonist, PGF(2alpha), and its selective analogues, latanoprost and bimatoprost free acids are full agonists (produce more than 80% of the maximal contractile response to 5-HT) in human umbilical vein. The agonist potency (pEC(50)) order was PGF(2alpha) (6.01+/-0.05)>latanoprost free acid (5.65+/-0.07)=bimatoprost free acid (5.59+/-0.08). The contractile effects of PGF(2alpha) and latanoprost free acid were blocked competitively by the prostanoid FP-receptor antagonist, AL-8810. The antagonist potencies (pK(B)) of AL-8810 vs. PGF(2alpha) (5.93+/-0.05) and vs. latanoprost free acid (6.40+/-0.08) in human umbilical vein are in good agreement with its ability to antagonize prostanoid FP receptors of rat, mouse and human cells. In all samples, clear signal was detected for cDNA amplification of prostanoid FP receptor and the specific prostanoid FP-receptor antibody recognized a protein of approximately 64 kDa. In conclusion, taking into account the obtained functional and biochemical data, we propose for the first time that human umbilical vein express prostanoid FP-receptors and these receptors could be involved in the vasoconstriction action of PGF(2alpha) in this tissue.