741292-75-1Relevant articles and documents
Design and synthesis of arylnaphthalene lignan lactone derivatives as potent topoisomerase inhibitors
Chen, Wang,Feng, Zili,Hu, Daihua,Meng, Jin
, p. 856 - 865 (2021/10/21)
Background: Arylnaphthalene lignan lactones are a class of natural products containing the phenyl-naphthyl skeleton. Some arylnaphthalene lignan lactones have been used in clinical practice as antitumor agents, due to their cytotoxicity and inhibitory activities against DNA topoisomerase I (Topo I) and topoisomerase II (Topo II). Objective: This study presents the design and synthesis of arylnaphthalene lignan lactones derivatives. The inhibitory activities against Topo I and Topo IIα and antitumor activities of these compounds were assayed. Methods: A series of arylnaphthalene lignan lactones derivatives have been designed and synthesized, using the Diels-Alder reaction and Suzuki reaction as the key steps. Their antiproliferation activities were evaluated by sulforhodamine B assay on human breast cancer MDAMB-231, MDA-MB-435 and human cervical cancer HeLa cells. DNA relaxation assays were employed to examine the inhibitory activity of compounds 1-22 on Topo I and Topo IIα in vitro. Flow cytometry analysis was performed to study the drug effects on cell cycle progressions. Results: Seven compounds exhibited the modest anti-proliferation activity with IC50 values between 1.36 and 20 μM. Compounds 3, 19 and 22 showed potent inhibitory activities with IC50 values less than 1 μM. DNA relaxation assay revealed that compound 22 showed potent inhibitory activity against Topo IIα in vitro. Compound 22 also induced DNA breaks in MDA-MB-435 cells evidenced by comet tails and the accumulation of γ-H2AX foci. The ability of 22 in inducing DNA breaks mediated by Topo IIα resulted in G2/M phase arrest and apoptosis. Conclusion: This work indicates that arylnaphthalene lignan lactones derivatives represent a novel type of Topo IIα inhibitory scaffold for developing new antitumor chemotherapeutic agents.
Photoinduced Molecular Transformations. Part 135. New Synthesis of Taiwanin C and Justicidin E based on a Radical Cascade Process involving β-Scission of Alkoxy Radicals generated from 3- and 8-Aryl-1-ethyl-1,2-dihydrocyclobutanaphthalen-1-ols prepared by Thermolysis of (Z)-tert-...
Kobayashi, Kazuhiro,Kanno, Yoshikazu,Seko, Shinzo,Suginome, Hiroshi
, p. 3111 - 3118 (2007/10/02)
A new general synthesis of naturally occuring phthalide lignans, based on a radical cascade process triggered by a regioselective β-scission of the alkoxy radicals generated by photolysis of the hypoiodites of 8-aryl-1-ethyl-1,2-dihydrocyclobutanaphthalen-1-ols, is described.Two phases are involved in the present synthesis of phthalide lignans; the first is a new general synthesis of tert-butyl 4-aryl-3- and 4-aryl-8-aminonaphthalene-2-carboxylates by an electrocyclic reaction of o-quinonedimethides thermally generated from (Z)-tert-butyl 3-amino-3-(bicycloocta-1,3,5-trien-7-yl)propenoates; the second is a transformation of the protected 4-aryl-3-aminonaphthalene-2-carboxylic acids into the phthalide lignans.This latter phase involves their successive conversions into 3- and 8-arylcyclobutanaphthalen-1(2H)-ones via the formation of a benzyne intermediate, and then into 3- and 8-aryl-1-ethyl-1,2-dihydrocyclobutanaphthalen-1-ols, followed by β-scission of the alkoxy radicals generated by photolysis of their hypoiodites, generated in situ with the mercury(II) oxide-iodine reagent in benzene.Simultaneous syntheses of the naturally occuring phthalide lignans taiwanin C and justicidin E were thus achieved.
