Synthesis and biological evaluation of 4-hydroxy-5-oxo-2, 5-dihydro-1H-pyrrole-3-carboxamides and their zinc(ii) complexes as candidate antidiabetic agents. (2nd June 2017)

• Record Type: Journal Article
• Authors: Saito, Ryota; Tamura, Moe; Kawano, Saya; Yoshikawa, Yutaka; Kato, Akihiro; Sasaki, Kaname; Yasui, Hiroyuki
• Is Part Of: New journal of chemistry. Volume 41:Number 13(2017)
• Page Start: 5572
• Page End: 5581
• Publication Date: 2017-06-02
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj00970d
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Five new zinc(ii ) complexes with 4-hydroxy-5-oxo-2, 5-dihydro-1 H -pyrrole-3-carboxamides were synthesized, and four of them exhibited insulin-mimetic activity in vitro . Abstract : The newly designed 1-(arylmethyl)-2, 5-dihydro-4-hydroxy-5-oxo-1 H -pyrrole-3-carboxamides (1a–e ) were synthesized by using N -tritylated acrylamide as a starting material, and their zinc(ii ) complexes (10a–e ) were readily prepared by simply mixing1a–e and ZnSO4 in the presence of LiOH. The aldose reductase (AR) inhibitory activity of1a–e was evaluated to reveal important structural features for 2, 5-dihydro-5-oxo-1 H -pyrrole derivatives to exhibit high AR inhibitory activity. The in vitro insulin–mimetic activity of these complexes was evaluated from 50% inhibitory concentrations (IC50 ) on free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. Four out of the five newly synthesized complexes exhibited higher in vitro insulin-mimetic activities than ZnSO4, a positive control. This study proved that the newly synthesized N2 O2 -coordination-type zinc(ii ) complexes based on pyrrole-3-carboxamide derivatives (1a –d ) are potential hypoglycemic agents.