Peptide conjugates of 18β-glycyrrhetinic acid as potent inhibitors of α-glucosidase and AGEs-induced oxidation

• DOI: 10.1016/j.ejps.2021.106045
• Publication Date: 2021-10-19T04:41:27Z
• Authors: Sadiq Noor Khan; Farzana Shaheen; Umair Aleem; Sumbla Sheikh; Alfred Ngenge Tamfu; Sajda Ashraf; Zaheer Ul-Haq; Saeed Ullah; Atia-tul- Wahab; M. Iqbal Choudhary; Humera Jahan
• Keywords: Conjugate; IC50; Tripeptide; Acarbose; Mixed inhibition; Moiety

18β-Glycyrrhetinic acid (18β-GA) is known for several biological activities, and has been the focus of extensive research development therapeutic agents. In current study, 18β-GA-peptide conjugates 2-11 were evaluated their in vitro α-glucosidase inhibitory antiglycation activities. Structure-activity relationship (SAR) established molecular interactions active bioconjugates with enzyme's binding sites predicted through modeling approach. tripeptide moiety 2-11, peptide residue at position 1 was found to have a significant role on inhibition. The most 5 (18β-GA-Cys1-Tyr2-Gly3), 8 (18β-GA-Pro1-Tyr2-Gly3) exhibited several-fold potent inhibition (IC50 values 20-28 μM), as compared standard drug acarbose = 875.8 ± 2.10 µM). Kinetic studies compounds, 4-8 revealed that conjugate exhibits competitive-type inhibition, while 6-8 showed non-competitive type simulation also supported kinetic results (18β-GA-Cys1-Tyr2-Gly3) inhibits enzyme by blocking its substrate site. AGEs-induced NO• inhibitors play an important controlling inflammation associated diabetes mellitus. using RAW 264.7 macrophage cell line. Our data 7-10 more inhibitors, comparable standards rutin, PDTC. (a competitive inhibitor α-glucosidase) strong activity against production. Furthermore, non-cytotoxic mouse fibroblast NIH-3T3, murine macrophages lines. conclusion, our demonstrates besides possessing newly synthesized alleviated production macrophages. Dual enzyme, qualify them further anti-diabetic discovery.