Khan, Sadiq Noor published the artcilePeptide conjugates of 18¦Â-glycyrrhetinic acid as potent inhibitors of ¦Á-glucosidase and AGEs-induced oxidation, SDS of cas: 71989-31-6, the publication is European Journal of Pharmaceutical Sciences (2022), 106045, database is CAplus and MEDLINE.
18¦Â-Glycyrrhetinic acid (18¦Â-GA) is known for several biol. activities, and has been the focus of extensive research for the development of therapeutic agents. In the current study, 18¦Â-GA-peptide conjugates 2-11 were evaluated for their in vitro ¦Á-glucosidase inhibitory and antiglycation activities. Structure-activity relationship (SAR) established and mol. interactions of active bioconjugates with the enzyme¡äs binding sites were predicted through mol. modeling approach. In tripeptide moiety of conjugates 2-11, peptide residue at position 1 was found to have a significant role on ¦Á-glucosidase inhibition. The most active 18¦Â-GA-peptide conjugates 5 (18¦Â-GA-Cys1-Tyr2-Gly3), and 8 (18¦Â-GA-Pro1-Tyr2-Gly3) exhibited several-fold potent ¦Á-glucosidase inhibition (IC50 values 20-28 ¦¬M), as compared to standard drug acarbose (IC50 = 875.8 ¡À 2.10 ¦¬M). Kinetic studies of potent compounds, 4-8 revealed that conjugate 5 exhibits competitive-type of inhibition, while conjugates 6-8 showed a non-competitive type of inhibition. The simulation studies also supported the kinetic results that conjugate 5 (18¦Â-GA-Cys1-Tyr2-Gly3) inhibits the ¦Á-glucosidase enzyme by blocking its substrate binding site. AGEs-induced NO? inhibitors play an important role in controlling the inflammation associated with diabetes mellitus. The peptide conjugates 2-11 were also evaluated in vitro for AGEs-induced NO? inhibition using RAW 264.7 macrophage cell line. Our data revealed that conjugates 7-10 were the more potent AGEs-induced NO? inhibitors, comparable to standards rutin, and PDTC. The peptide conjugate 5 (a competitive inhibitor of ¦Á-glucosidase) also exhibited a strong inhibitory activity against AGEs-induced NO? production Furthermore, peptide conjugates 2-11 were found non-cytotoxic to mouse fibroblast NIH-3T3, and murine macrophages RAW 264.7 cell lines. In conclusion, our data demonstrates that besides possessing strong ¦Á-glucosidase inhibition, the newly synthesized peptide conjugates also alleviated the AGEs-induced NO? production in RAW macrophages. Dual inhibition of ¦Á-glucosidase enzyme, and AGEs-induced NO? production by 18¦Â-GA-peptide conjugates qualify them for further research in anti-diabetic drug discovery.
European Journal of Pharmaceutical Sciences published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, SDS of cas: 71989-31-6.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia