Synthesis, Crystal Structure, Anti-inflammatory and Anti-hyperglycemic Activities of Novel 3,4-Disubstituted 1,2,4-Triazol-5(4H)-one Derivatives

Title:Synthesis, Crystal Structure, Anti-inflammatory and Anti-hyperglycemic Activities of Novel 3,4-Disubstituted 1,2,4-Triazol-5(4H)-one Derivatives

Volume: 10 Issue: 8

Author(s): Muhammad Saleem, Seon-Mi Yu, Muhammad Rafiq, Song-Ja Kim, Sung-Yum Seo and Ki Hwan Lee

Affiliation:

Keywords: Dyehydrocyclization, α-glucosidase inhibition, α-amylase inhibition, collagen type II, COX-2, single crystal XRD.

Abstract: A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-, tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5ar) were characterized by IR, ¹H NMR and ¹³C NMR analyses. The structure of one compound 5a was determined by single crystal X-ray diffraction analysis. All of the synthesized compounds were screened for their anti-inflammatory and anti-diabetic (α-glucosidase and α-amylase inhibition) activity to identify new drugs that might be useful in preventing damage related to diabetes and inflammation. Compounds 5j, 5k and 5m decrease the expression of type II collagen in a dose dependent manner; similarly 5l decrease the COX-2 expression of rabbit articular chondrocytes in a dose dependent manner possessing potent anti-inflammatory potential while some of derivatives including 5c, 5e, 5g and 5h cause inflammation. Meanwhile, excellent α-glucosidase and moderate α-amylase inhibitory profiles against carbohydrate modulating enzymes were demonstrated by compounds 5b, 5f, 5k and 5q compared to the reference standard acarbose, and compounds 5g, 5h, 5i, 5j, 5l and 5o exhibited moderate to low enzyme inhibition potential among the series.

Cite this article as:

Saleem Muhammad, Yu Seon-Mi, Rafiq Muhammad, Kim Song-Ja, Seo Sung-Yum and Lee Hwan Ki, Synthesis, Crystal Structure, Anti-inflammatory and Anti-hyperglycemic Activities of Novel 3,4-Disubstituted 1,2,4-Triazol-5(4H)-one Derivatives, Medicinal Chemistry 2014; 10 (8) . https://dx.doi.org/10.2174/1573406410666140327142912