alpha-Glucosidase inhibitory antihyperglycemic activity of substituted chromenone derivatives.
Series of 3,4- and 3,6-disubstituted chromenones including new chromenone derivatives were synthesized applying various synthetic strategies including Pechmann condensation, Knoevenagel condensation, Reimer-Tiemann reaction and Suzuki coupling in very good yields. Synthesized compounds (4a-z) were screened for in vitro alpha-glucosidase inhibitory and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. Majority of compounds displayed varying degrees of alpha-glucosidase inhibitory and DPPH scavenging activity. Compound 4x emerged as the most potent alpha-glucosidase inhibitor in present series of compounds owing to the presence of 3-acetyl-6-(6-methoxy-3-pyridyl) group on chromenone; however, it could not display DPPH scavenging activity and was found to be mixed non-competitive type inhibitor of rat intestinal alpha-glucosidase. When tested in vivo for antihyperglycemic activity in starch loaded Wistar rats, it displayed significant antihyperglycemic property. This is the first report assigning rat intestinal alpha-glucosidase inhibitory property for this class of new chromenones and presents new family of compounds possessing alpha-glucosidase inhibitory activities and antihyperglycemic property. Compound 4x may serve as an interesting new compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.
Raju
B China
BC
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India. chinarajuiict@yahoo.co.in
Tiwari
Ashok K
AK
Kumar
J Ashok
JA
Ali
A Zehra
AZ
Agawane
Sachin B
SB
Saidachary
G
G
Madhusudana
K
K
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D007422:Intestines / Q000201:enzymology; D008297:Male; D010851:Picrates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000520:alpha-Glucosidases / Q000378:metabolism
D001578:Benzopyrans; D001713:Biphenyl Compounds; D001786:Blood Glucose; D016166:Free Radical Scavengers; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; D000520:alpha-Glucosidases