Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)

► Piplartine, isolated from Piper chaba, inhibited ALR2. ► Piplartine analogues are synthesized by Michael addition with improved efficacy. ► The analogues: 3c, 3e and 2j displayed potent ARI activity. ► These compounds also suppressed sorbitol accumulation in red blood cells. ► SAR analysis and docking studies of piplartine support these claims.