Hyperkouytones A—O, New Polyprenylated Acylphloroglucinols from <i>Hypericum kouytchense</i> with Multidrug Resistance Reversal Activity

Comprehensive Summary Given the lack of systematic polyprenylated acylphloroglucinols (PPAPs) research on traditional Chinese medicine of Hypericum kouytchense , this plant was applied for the phytochemical study, which led to fifteen new PPAPs ( 1 — 15 , PPAPs), along with 36 known PPAP derivatives. Their structures and absolute configurations were established by comprehensive spectral analysis and theoretical ECD and NMR calculations. Structurally, compound 1 possesses a rare fused 6/6/6/5/5 pentacyclic ring system. Eleven compounds exhibited good multidrug resistance reversal activity (RF ranging from 5 to 53) in HepG2/ADR cells. Importantly, compound 34 , the most potential MDR modulator, showed better reversal effect (RF: 53) than positive control, verapamil. The primary mechanistic study of compound 34 , implied that this compound could prohibit the function of P‐gp transport rather than its expression. The possible recognition mechanism between compound 34 and P‐gp was predicted by molecular docking.