Uracil Substitution on a Hippuric Acid Containing 1,3,4-thiadiazole Scaffold: The Exploration of the Anti-Hyperglycaemic Potential

Abstract

The human civilization has witnessed diabetes mellitus as a curse which has already affected 400 million individuals and is expected to affect 600 million people by the end of 2030. Compromised pharmacokinetics, reduced pharmacological efficacy, etc. of the modern-day drugs has motivated researchers across the world to look for better alternatives. 1,3,4thiadiazoles have been rising as a prominent scaffold in reducing the blood glucose level through various mechanisms. While moving towards the glorified path of drug design, a novel molecule with anti-diabetic interest was developed with an intention of having a better pharmacological profile than the existing drugs by substituting a uracil moiety at 5th position of a hippuric acid containing 1,3,4-thiadiazole scaffold and screened using streptozotocin-induced hyperglycemic method in Swiss albino rats. The uracil-containing 1,3,4-thiadiazole expressed an impressive hypoglycemic activity with a 28.89% reduction in the blood glucose level at 6 hrs. The compound also exhibited comparable pharmacological activity with that of the standard drug glibenclamide (39.12%) at 6 hrs. The compound may be believed to successfully reduce the glucose level by either an expression of PPAR-γ or inhibition of α-glucosidase. The research has opened new prospects in the rational designing of the next generation antihyperglycemic drug molecules with pronounced pharmacodynamics and pharmacokinetic effects.