(±)-2-Cyclohexyl-5-methoxy-2H-chromene, a Synthetic 5-Methoxyflavone Derivative, Is a Selective DNA Polymerase-β Inhibitor with Neuroprotective Activity against β-Amyloid Toxicity.

ABSTRACT: DNA polymerase-β (DNA pol-β) plays a critical role in β-amyloid-induced neurodegeneration by mediating aberrant DNA replication in postmitotic neurons. In previous work, we demonstrated that 5-methoxyflavone inhibits DNA pol-β, though computational analyses suggested potential binding to the primase p58 subunit. Through molecular modeling, here, we designed (S)-2-cyclohexyl-5-methoxy-2H-chromene (S-chromene), a novel flavone-derived inhibitor exhibiting strong electrostatic complementarity with DNA pol-β but weak interaction with primase p58, suggesting enhanced selectivity. (R)-2-cyclohexyl-5-methoxy-2H-chromene (R-chromene) exhibited indistinguishable binding properties from S-chromene. The compound was obtained as a racemic mixture (chrom

SUBMITTER: Guccione S 

PROVIDER: S-EPMC12784329 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature