title: Synthesis of novel poly-hydroxyl functionalized acridine derivatives as inhibitors of α-Glucosidase and α-Amylase.
abstract: In this study a novel series of poly-hydroxyl functionalized acridine derivatives (L1-L9) was synthesized and their inhibitory activities against α-Glucosidase (α-Gls) and α-Amylase (α-Amy) were evaluated, spectroscopically. The synthetic compounds consist of three different substructures, including a 4-(4-aminophenoxy) phenyl group (R3), an acridine moiety (R2) and a poly-hydroxy chain (R1). The results indicate that among the synthetic compounds, L5 with a chromeno[3',4':5,6]pyrido[2,3-d]pyrimidine moiety demonstrates the highest inhibitory activity against both yeast and rat α-Gls enzymes. Also, L2 with the thioxo-pyrido[2,3-d:6,5-d'] dipyrimidine moiety plays an important role in the inhibition of yeast α-Gls. In addition, the results may suggest a significant role for the nature of sugar moiety of the synthetic compounds in their inhibitory action against α-Gls. Moreover, in comparison with Acarbose, which is a widely used anti-diabetic drug, these compounds show negligible inhibitory activity against pancreatic α-Amy, which is important in the term of their reduced susceptibility for possible development of the intestinal disturbance side effects. Results of this study may suggest these synthetic compounds as novel molecular templates for construction of potentially anti-diabetic drugs with the ability for more convenient management of postprandial hyperglycemia.
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toobaei
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran; Institute of Biotechnology, Shiraz University, Shiraz, Iran. Electronic address: ryousefi@shirazu.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Panahi
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Shahidpour
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nourisefat
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Doroodmand
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: khalafi@chem.susc.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Khalafi-Nezhad
mesh_terms: D000166:Acridines / Q000138:chemical synthesis*; D000818:Animals; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007700:Kinetics; D008958:Models, Molecular; D010179:Pancreas / Q000201:enzymology; D051381:Rats; D015003:Yeasts / Q000201:enzymology; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000520:alpha-Glucosidases / Q000737:chemistry
chemical_list: D000166:Acridines; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D000516:alpha-Amylases; D000520:alpha-Glucosidases
keywords: Anti-diabetic compounds; Inhibition; Postprandial hyperglycemia; α-Amylase; α-Glucosidase