Several 15,16-epoxy-8,13,14-labdatriene derivatives modified at the C-16 position with a 1,2,4-oxadiazole ring with various substituent in the 5-th position, were obtained via multistep synthesis from 16-formyl derivatives of natural diterpenoid lambertianic acid. The cytotoxicity of furanolabdanoid-based 1,2,4oxadiazoles was evaluated against human cancer cells (CEM-13, MT-4, U-937, MCF-7, MDA-MB-231, MEL-8) using the conventional MTT assays. All the tested diterpenoid-oxadiazole hybrids displayed better cytotoxic activity then lambertianic acid. The activity and selectivity to the cell line increased even further in the compounds containing a chloromethyl substituent in the 5th position of the 1,2,4-oxadiazole ring. Two of the synthesized compounds exhibited high cytotoxic activity against lymphoblastoid cell line CEM-13 (GI 50 0.08-0.34 mM), which was higher that than of the comparative drug Doxorubicin. The antitumor mechanism may be related to apoptosis induction in U-937, MCF-7, and CEM-13 cells.[a] Dr.
A series of new analogs of combretastatin A-4 (CA-4, 1) with the A or B-ring replaced by a 3-oxo-2,3-dihydrofurocoumarin or a furocoumarin residue have been designed and synthesized by employing a cross-coupling approach. All the compounds were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, MT-4, U-937) using conventional MTT assays. Structure-activity relationship analysis reveals that compounds 2, 3, 6-8 in which the (Z)-styryl substituent was connected to the 2-position of the 3-oxo-2,3-dihydrofurocoumarin core, demonstrated increased potency compared to 3-(Z)-styrylfurocoumarins 4, 5, 9-11. The methoxy-, hydroxyl-and formyl-substitution on the aromatic ring of the (Z)-styryl moiety seems to play an important role in this class of compounds. Compounds 2 and 3 showed the best potency against the CEM-13 cell lines, with CTD 50 values ranging from 4.9 to 5.1 μM. In comparison with CA-4, all synthesized compounds presented moderate cytotoxic activity to the T-cellular human leucosis cells MT-4 and lymphoblastoid leukemia cells CEM-13, but most of them were active in the human monocyte cell lines U-937.
Twenty-one phenolic compounds (1-21) including dihydrocinnamic acid, isoflavonoids, flavonoids, coumestans, pterocarpans, chalcones, isoflavan and isoflaven, were isolated from the roots of Glycyrrhiza pallidiflora Maxim. Phloretinic acid (1), chrysin (6), 9-methoxycoumestan (8), isoglycyrol (9), 6″-O-acetylanonin (19) and 6″-O-acetylwistin (21) were isolated from G. pallidiflora for the first time. Isoflavonoid acetylglycosides 19, 21 might be artefacts that could be produced during the EtOAc fractionation process of whole extract. Compounds 2-4, 10, 11, 19 and 21 were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, MT-4, U-937) using the conventional MTT assays. Isoflavonoid calycosin (4) showed the best potency against human T-cell leukaemia cells MT-4 (CTD, 2.9 μM). Pterocarpans medicarpin (10) and homopterocarpin (11) exhibit anticancer activity in micromolar range with selectivity on the human monocyte cells U-937. The isoflavan (3R)-vestitol (16) was highly selective on the lymphoblastoid leukaemia cells CEM-13 and was more active than the drug doxorubicin.
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