Flavonol tri- and tetraglycosides from Albizia guachapele Baker: isolation and biological evaluation.

Phytochemical investigation of the leaves of Albizia guachapele Baker (Fabaceae) led to the isolation and identification of two previously unreported kaempferol tetraglycosides, designated Guachapins A and B, together with ten known compounds. Their structures were established by interpretation of spectral data, including UV, ESI-MS, and NMR as kaempferol-3-O-β-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→6)-O-[α-l-rhamnopyranosyl-(1→2)]-β-d-galactopyranoside, namely Guachapin A (3) and kaempferol-3-O-β-d-glucopyranosyl-[6-O-E-feruloyl]-(1→4)-α-l-rhamnopyranosyl-(1→6)-O-[α-l-rhamnopyranosyl-(1→2)]-β-d-galactopyranoside, namely Guachapin B (4). To provide mechanistic context for the antiproliferative activity of the major known isolate, mauritianin (1), a Topo II-focused in silico and cell-based mechanistic evaluation was conducted here for the first time for this compound. Compound 1 was initially evaluated through molecular docking and molecular dynamics (MD) simulation against topoisomerase II (Topo II), revealing a stable and favorable binding interaction at the enzyme's active site. These findings were further supported by in vitro assessment of Topo II alpha protein expression, which revealed a concentration-dependent reduction in intracellular Topo II alpha levels. Collectively, these convergent in silico and cell-based findings identify compound 1 as a Topo II-related antiproliferative lead candidate, displaying a phenotypic profile (G2/M arrest and predominant late apoptosis) consistent with a Topo II-mediated mechanism of cytotoxicity. Direct mechanistic confirmation through enzymatic and DNA damage assays is identified as a priority for future investigation.