Flavanols from Tetrapleura tetraptera with cytotoxic activities

Tetrapleura tetraptera is a medicinal plant used in East and West Africa to treat inflammation and related diseases. From the stem bark of the plant, three previously undescribed flavan-3-ol derivatives named (2R,3S)-3,3',5',7-tetrahydroxy-4'-methoxyflavane (1), (2R,3S)-3',5',7-trihydroxy-4'-methoxyflavane-3-O-β-D-glucopyranoside (2), and (2R,3S,4S)-3,3',4,5',7-pentahydroxy-4'-methoxyflavane (3) were isolated with three known analogues. The structural elucidation of the compounds was performed based on NMR spectroscopy and HRMS data analyses. The absolute configurations around the stereogenic carbons were determined using Circular Dichroism (ECD) and density functional theory (DFT) calculations. The cytotoxicity of the isolated compounds was tested using resazurin reduction assay. Compound 1 was moderately active against both recalcitrant leukemia cell lines with IC₅₀ values of 21.90 μM towards CCRF-CEM and 50.80 towards CEM/ADR5000. Similar level of activity was observed for compound 3 against CCRF-CEM cell line, IC₅₀ = 35.50 μM. All the tested compounds were not cytotoxic compared with the standard drug, doxorubicin, with IC₅₀ values of 0.0075 against CCRF-CEM and 24.30 μM against CEM/ADR5000.