Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue – Synthesis and structure–activity studies

Synthesis of a new series of urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole has been reported. Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity. Several compounds showed promising activity with IC50 < 5 μM compared to standard rutin (IC50 = 41.9 μM). Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity. Thus, the title compounds represent novel class of potent antiglycating agents.

Graphical abstractThis article reports the synthesis, characterization and antiglycation activity of the ureido and thioureido derivatives of Gly/Pro conjugated heterocycle.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights▶ Synthesis of novel urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole. ▶ In vitro antiglycation activity. ▶ Several compounds containing –OCH3 and –Br substituents found to be highly active. ▶ Structure–activity relationship has been discussed.