Refine
Has Fulltext
- no (2)
Year of publication
- 2019 (2) (remove)
Document Type
- Article (2) (remove)
Language
- English (2)
Is part of the Bibliography
- yes (2)
Keywords
- DFT calculations (1)
- Leguminosae (1)
- Lonchocarpus bussei (1)
- Lonchocarpus eriocalyx (1)
- NMR spectroscopy (1)
- conformational analysis (1)
- cycloaddition (1)
- cytotoxicity (1)
- isoflavone (1)
- modified Mannich reaction (1)
- ortho-quinone methide (o-QMs) (1)
- pterocarpan (1)
Institute
A new isoflavone, 4′-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2′-dimethoxy-3′,4′-methylenedioxyisoflavone, 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol. (6aR,11aR)-Edunol was also isolated from the stem bark of L. eriocalyx. The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC50 values below 10 μM were observed for the isoflavones 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells; for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant breast adenocarcinoma MDA-MB231/BCRP cells and resistant gliobastoma U87MG.ΔEGFR cells.
To synthesize functionalized Mannich bases that can serve two different types of ortho-quinone methide (o-QM) intermediates, 2-naphthol and 6-hydroxyquinoline were reacted with salicylic aldehyde in the presence of morpholine. The Mannich bases that can form o-QM and aza-o-QM were also synthesized by mixing 2-naphthol, 2-nitrobenzaldehyde, and morpholine followed by reduction of the nitro group. The highly functionalized aminonaphthol derivatives were then tested in [4+2] cycloaddition with different cyclic imines. The reaction proved to be both regio- and diastereoselective. In all cases, only one reaction product was obtained. Detailed structural analyses of the new polyheterocycles as well as conformational studies including DFT modelling were performed. The relative stability of o-QMs/aza-o-QM were also calculated, and the regioselectivity of the reactions could be explained only when the cycloaddition started from aminodiol 4. It was summarized that starting from diaminonaphthol 25, the regioselectivity of the reaction is driven by the higher nucleophilicity of the amino group compared with the hydroxy group. 12H-benzo[a]xanthen-12-one (11), formed via o-QM formation, was isolated as a side product. The proton NMR spectrum of 11 proved to be very unique from NMR point of view. The reason for the extreme low-field position of proton H-1 could be accounted for by theoretical calculation of structure and spatial magnetic properties of the compound in combination of ring current effects of the aromatic moieties and steric compression within the heavily hindered H(1)-C(1)-C(12b)-C(12a)-C(12)=O structural fragment.