chrysosplenetin-b and artemetin

The chemical investigation of the bioactive nonpolar fractions of Tanacetum gracile afforded two flavonoid analogues namely, 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (1) and 5,4'-dihydroxy-3,6,7,3',4'-tetramethoxyflavone (2) which were identical to the previously reported artemetin and chrysosplenetin respectively. The structure of the compounds was elucidated on the basis of spectroscopic evidences and they showed significant cytotoxic activity against human breast cancer cells (MCF-7 and T47D). Mechanism based study showed that the compounds modulated microtubule depolymerization by activating mitotic spindle checkpoint. Molecular docking at the colchicine binding pocket revealed that the compounds bind at α-β interfacial site of tubulin, correlating binding interactions with probable inhibition mechanism. The study reveals important observations to generate improved flavonoids that leads to cell apoptosis. The compounds were also evaluated for absorption, metabolism and toxicity by online webserver admetSAR. The significant microtubule disassembling property and less toxicity paves way for consideration of the compounds as chemopreventive agents.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Binding Sites; Blood-Brain Barrier; Breast Neoplasms; Colchicine; Drug Screening Assays, Antitumor; Female; Flavonoids; Humans; MCF-7 Cells; Membrane Potential, Mitochondrial; Microtubules; Molecular Docking Simulation; Molecular Structure; Rats; Reactive Oxygen Species; Tanacetum; Tubulin Modulators

To study the chemical constituents of Artemisia rupestris.. The chemical constituents were isolated by column chromatography on silical gel and sephadex LH - 20. Their structures were elucidated on the basis of spectral analysis.. 8 compounds have isolated from this plant, and the structures of them have identified as rupestonic acid (1), chrysosplenetin B (2), artemetin (3), herniarin (4), isokaempferide (5), vanillic acid (6), kaempferol 3, 3', 4'-trimethyl ether (7) and ermanine (8).. Compounds 2-8 have been isolated from this plant for the first time.

Topics: Artemisia; Flavonoids; Plants, Medicinal; Umbelliferones