- Synthesis and biological evaluation of new 4β-anilino- and 4β-imido-substituted podophyllotoxin congeners
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A series of C-4-anilino- and C-4-imido-substituted new podophyllotoxin congeners have been designed, synthesized, and evaluated for their cytotoxicity and DNA topoisomerase-II (topo-II) inhibition potential. Some of these compounds have exhibited promisin
- Kamal, Ahmed,Gayatri, N. Lakshmi,Rajasekhar Reddy,Murali Mohan Reddy,Arifuddin,Dastidar, Sunanda G.,Kondapi, Anand K.,Rajkumar
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- Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin
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Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In the course of our ongoing investigation of quantitative structure-activity relationships to find biorational antitumor drugs, two series of pyridine acid ester derivatives of podophyllotoxin and 4′-demethylepipodophyllotoxin have been prepared by reacting the corresponding pyridine acids with the hydroxyl group of podophyllotoxin and 4′-demethyl epipodophyllotoxin in the presence of dimethylaminopyridine (DMAP) and N,N-dicyclohexylcarbodiimde (DCC). The structures of the compounds were extensively characterized by using 1H-nuclear magnetic resonance, mass spectroscopy, infrared, and elemental analysis and evaluated for their in vitro cytotoxicity on two neoplastic cell lines (P-388 murine leukemia, A-549 human lung carcinoma) using a MTT-based assay, the results indicated significantly higher efficacy of these compounds in comparison with the prototypical inhibitor etoposide. On the basis of the preliminary biological testing results, it suggested that the cytotoxic activity of OCH3 at C-4′ is more potent than that of its demethylated analogs and the podophyllotoxin substitution at C-4 may be optimal for synthesizing more potent cytotoxic compounds.
- Liu, Ying-Qian,Yang, Liu,Tian, Xuan
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p. 319 - 330
(2008/12/21)
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- ANTICANCER COMPOUNDS
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This invention features compounds having formula (I): wherein, R1, R 2,R3, R4, R6, R7, T, X, and Y are as defined herein. This invention also features a method for treating cancer. The method includes administrating to a subject in need thereof a compound of formula (I).
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- An efficient method for 4β-anilino-4'-demethylepipodophyllotoxins: Synthesis of NPF and W-68
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4β-Substituted podophyllotoxin congeners have been obtained with significant stereoselectivity and improved yields by employing Bu4N+I in the displacement reaction of the 4-bromoepipodophyllotoxin. The DNA topoisomerase II inhibitors, NPF and W-68 have been prepared in good yields by this method.
- Kamal,Gayatri
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p. 3359 - 3362
(2007/10/03)
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- New compounds related to podophyllotoxin and congeners: synthesis, structure elucidation and biological testing.
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4-Azido, 4-amino, 4-amido and 4-alkoxy compounds related to the lignans podophyllotoxin and 4'-demethylepipodophyllotoxin have been synthesized, and their structures elucidated. The Ritter reaction was shown to be useful in the preparation of the 4-amido compounds with the required stereochemistry. A preparative method for 4-chloro-4-deoxypicrophyllotoxin, for which all earlier synthetic attempts resulted in the two dehydrated compounds, alpha- and beta-apopicropodophyllotoxin, was developed. Supplementary preliminary studies of the biological activities of some of the compounds were performed. All compounds had pronounced inhibitory effect on the in vitro growth of human cervical cancer cells and TC-mouse cells with 4-amino-4-deoxypodophyllotoxin and 4-azido-4-deoxypodophyllotoxin showing the highest activity. Alkaline elution studies indicate that the toxicity of the 4'-demethoxy derivatives is due to protein-mediated DNA nicking. None of the compounds were found to have antiviral effect against herpes simplex type 2 (HSV-2), human immunodeficiency (HIV), and cytomegalovirus (CMV) in doses not toxic to the cells.
- Hansen,Jensen,Willumsen,Norskov-Lauritsen,Ebbesen,Nielsen,Buchardt
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p. 1190 - 1200
(2007/10/02)
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- Facile synthesis of thioglucose analogs of the anticancer agent etoposide
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Thioglucose-derived analogs of the clinical anticancer agent etoposide have been synthesized via a novel strategy of coupling the sugar and aglycone moieties.
- Showalter,Winters,Sercel,Michel
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p. 2849 - 2852
(2007/10/02)
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