biostudies-literatureWang EDepartment of Education of Guizhou ProvinceNational Natural Science Foundation of China28098-28103https://www.ebi.ac.uk/biostudies/studies/S-EPMC9528730biostudies-literatureUnknown12(43)We report herein an efficient polyphosphoric acid (PPA) promoted one-pot protocol for the synthesis of flavanone derivatives from 2-hydroxyacetophenones and benzaldehydes. A variety of flavanones were produced in moderate to excellent yields and evaluated for their neuroprotective effects against <i>N</i>-methyl-d-aspartate (<i>N</i>MDA)-induced excitotoxicity in PC12 cells. Derivatives bearing electron-donating groups exhibited better neuroprotective activity. Compound 3m demonstrated the best protective potency and reversed the intracellular calcium (Ca²⁺) influx caused by NMDA, suggesting that flavanones protected the PC12 cells against NMDA-induced neurotoxicity <i>via</i> inhibition of Ca²⁺ overload.RSC advancesPolyphosphoric acid-promoted one-pot synthesis and neuroprotective effects of flavanones against NMDA-induced injury in PC12 cells.PMC952873081860609QJHKYZ[2020]018Yang XYang LLuo JGan MLei YWang ESong SYang QWang XYang FfalsePolyphosphoric acid-promoted one-pot synthesis and neuroprotective effects of flavanones against NMDA-induced injury in PC12 cells.We report herein an efficient polyphosphoric acid (PPA) promoted one-pot protocol for the synthesis of flavanone derivatives from 2-hydroxyacetophenones and benzaldehydes. A variety of flavanones were produced in moderate to excellent yields and evaluated for their neuroprotective effects against <i>N</i>-methyl-d-aspartate (<i>N</i>MDA)-induced excitotoxicity in PC12 cells. Derivatives bearing electron-donating groups exhibited better neuroprotective activity. Compound 3m demonstrated the best protective potency and reversed the intracellular calcium (Ca²⁺) influx caused by NMDA, suggesting that flavanones protected the PC12 cells against NMDA-induced neurotoxicity <i>via</i> inhibition of Ca²⁺ overload.2022-01-01T00:00:00Z2022 Sep2026-05-31T16:00:06.057Z2025-04-04T12:46:04.192ZS-EPMC95287303632027510.1039/d2ra03562f