- Design and synthesis of arylnaphthalene lignan lactone derivatives as potent topoisomerase inhibitors
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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.
- Chen, Wang,Feng, Zili,Hu, Daihua,Meng, Jin
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p. 856 - 865
(2021/10/21)
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- Palladium-promoted [2 + 2 + 2] cocyclization of arynes and unsymmetrical conjugated dienes: Synthesis of justicidin B and retrojusticidin B
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A facile synthesis of natural and unnatural arylnaphthalenes has been demonstrated via the unprecedented palladium-promoted [2 + 2 + 2] cocyclization of arynes and unsymmetrical conjugated dienes using the N-heterocyclic carbene as a ligand. The unsymmetr
- Patel, Ramesh M.,Argade, Narshinha P.
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supporting information
p. 14 - 17
(2013/03/28)
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- A new benzannulation reaction and its application in the multiple parallel synthesis of arylnaphthalene lignans
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A new aromatic annulation reaction based on sequential Horner-Emmons and Claisen condensation reactions is described. The method is high yielding and provides a rapid entry to arylnaphthalenes. The lignan natural products justicidin B 1, retrojusticidin B 2, taiwanin C 3, justicidin E 4, chinensin 5 and retrochinensin 6 have all been synthesised in good overall yield using this protocol, demonstrating its potential in multiple parallel synthesis. The selective oxidation of diols 34-36 to the corresponding retrolactones with barium manganate(VI) is also noteworthy.
- Flanagan, Stuart R,Harrowven, David C,Bradley, Mark
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p. 5989 - 6001
(2007/10/03)
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- DDQ-Cyclodehydrogenation: Syntheses of 1-Phenylnaphthalenic Lignans
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1,2-Diarylidenesuccinic anhydrides (Ia-c) when refluxed with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) and dry HCl in anhyd. benzene undergo cyclization to give 1-phenylnaphthalene-2,3-dicarboxylic anhydrides (IIa-d) in 65-70percent yields.Starting from the anhydrides IIc and IId, syntheses of retochinensin (Vc), chinensin (VIc), retrojusticidin-B (Vd) and justicidin-B (VId) have been achieved.
- Satyanarayana, P.,Rao, P. Koteswara
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p. 151 - 153
(2007/10/02)
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