New Compounds Related to Podophyllotoxin and Congeners: Synthesis, Structure Elucidation and Biological Testing.

Hansen, Henrik F.; Jensen, R. B.; Willumsen, Agnes M.; Nørskov‐Lauritsen, Niels; Ebbesen, Peter; Nielsen, Peter; Buchardt, Ole

doi:10.3891/acta.chem.scand.47-1190

Cited by 38 publications

(24 citation statements)

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“…The configuration at the C-4 position for compounds 5a-5f and 8a-8f was assigned on the basis of their J 3, 4 coupling constants. The C-4a-substituted compounds have a J 3, 4 !8.5 Hz as H-3 is trans to H-4, whereas C-4b-substituted compounds have a J 3, 4 <4.5Hz, owing to the cis relationship between H-3 and H-4 (Fred Brewer, 1979;Hansen et al, 1993). Moreover, the absence of C-4b isomers for compounds 5a-5f may be explained through the reaction mechanism involving the assistance of DCC in the presence of …”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Liu

Tian

2007

Med Chem Res

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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 0 -demethylepipodophyllotoxin have been prepared by reacting the corresponding pyridine acids with the hydroxyl group of podophyllotoxin and 4 0 -demethyl epipodophyllotoxin in the presence of dimethylaminopyridine (DMAP) and N,N-dicyclohexylcarbodiimde (DCC). The structures of the compounds were extensively characterized by using 1 H-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 OCH 3 at C-4 0 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.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Liu

Tian

2007

Med Chem Res

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“…For example, among the set of compounds with a perbutyrylated sugar moiety and a methoxyl group at the C-4'-position (compounds 26, 32 and 38), compound 38 with the longest linking spacer (six ethylene glycol repeating units) is the most active compound against four out of five cancer cell lines tested, followed by 32 which has a shorter linker (three ethylene glycol repeating units), and 26 which has no linking spacer in-between is the least active. However, among the set of compounds with a perbutyrylated sugar moiety and a hydroxyl group at the C-4'-position (compounds 29, 35 Previously, Reddy and co-workers [28] reported the cytotoxic activity of several 4β-triazole-linked sugar-podophyllotoxin conjugates. The cytotoxic potency of compound 42 against A-549 cells reported in their paper was quite similar to our data, however, our findings that peracetylation and perbutyrylation of the glucose residue lead to increased activity are different from their observation [28].…”

Section: Evaluation Of Biological Activitymentioning

confidence: 99%

“…The preparation of compound 18 has been described in literature [34]. To introduce the azido functionality for the click-reaction, podophyllotoxin was readily converted to 4β-azido-4-deoxypodophyllotoxin (7) and 4β-azido-4-deoxy-4'-demethypodophyllotoxin (8) according to known procedures [35,36].…”

Section: Chemical Synthesismentioning

confidence: 99%

Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings

Xu²,

et al. 2013

Molecules

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A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC 50 values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue.

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“…This compound 3 was formerly obtained by Kuhn et al, [2] according to a method involving the treatment with hydrogen bromide as a gas in methylene chloride=Et 2 O at 0 C, followed by a basic treatment (BaCO 3 ). This procedure was then routinely used by different groups, [3][4][5][6] giving an average yield of 40% in our hands and requiring long reaction and purification times. Daley et al [7] improved this reaction using ISiMe 3 .…”

Section: Introductionmentioning

confidence: 99%

Practical Demethylation of Podophyllotoxin and Efficient Preparation of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin

Guminski

Grousseaud

Cugnasse

et al. 2012

Synthetic Communications

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New Compounds Related to Podophyllotoxin and Congeners: Synthesis, Structure Elucidation and Biological Testing.

Cited by 38 publications

References 0 publications

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin

Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings

Practical Demethylation of Podophyllotoxin and Efficient Preparation of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin

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