An Investigation of the Antiviral Activity of Podophyllum peltatum

Bedows, Elliott; Hatfield, George M.

doi:10.1021/np50024a015

Cited by 81 publications

(50 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Berkin [62] and Hartwell and Shear [63] described the destructive effect of this resin on experimental cancer cells in animals. Similary the antiviral activity of an aqueous extract of Podophyllum peltatum has also been investigated [64]. The extract was fractionated by reverse-phase chromatography and podophyllotoxin was found to be the most active component in inhibiting the replication of measles and herpes simplex type 1 virus (HSV-1) [65].…”

Section: Podophyllotoxin Etoposide and Teniposidementioning

confidence: 99%

Antitumor Properties of Podophyllotoxin and Related Compounds

Gordaliza¹,

Ma²,

Jm³

et al. 2000

CPD

251

143

View full text Add to dashboard Cite

The lignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, lignans, and especially cyclolignans, have been the objective of numerous studies focused to prepare better and safer anticancer drugs. The mechanism by which podophyllotoxin blocks cell division is related to its inhibition of microtubule assembly in the mitotic apparatus. However, etoposide and teniposide were shown not to be inhibitors of microtubule assembly which suggested that their antitumor properties were due to another mechanism of action, via their interaction with DNA and inhibition of DNA topoisomerase II. Other podophyllotoxin derivatives has also been reported which retained or even improved the cytotoxic activity, but these were weak inhibitors of topoisomerase II in vitro; the data revealed that such analogs exhibit a different, as yet unknown, mechanism of action. The main deficiency of these compounds is their cytotoxicity for normal cells and hence side effects derived from their lack of selectivity against tumoral cells. In this regard it is necessary to investigate and prepare new more potent and less toxic analogs, that is, with better therapeutic indices. It is well accepted from structure-activity studies in this field that the trans-lactones are more potent as antineoplastics than the cis-lactones. Not only the configuration of the D ring is an important factor for high cytotoxic activity, but also a quasi-axial arrangement of the E ring is necessary. On this basis, studies on lignans have been addressed to modify the lactone moiety and prepare analogs with heteroatoms at different positions of the cyclolignan skeleton. Our group has been working during the last few years on chemical transformations of podophyllotoxin and analogs and we have prepared a large number of cyclolignan derivatives some of which display potent antiviral, immunosuppressive and cytotoxic activities. We have reported several new cytotoxic agents with nitrogen atoms at C-7 or C-9 or at both C-7 and C-9: imine derivatives, oxime derivatives, pyrazoline-, pyrazo- and isoxazoline-fused cyclolignans. At present, we are preparing mainly new compounds by modifications of the A and E cyclolignan-rings. They are being tested on cultures of different tumoral cell lines (P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma and MEL-28 human melanoma) and some of them have shown an interesting and selective cytotoxicity.

show abstract

Section: Podophyllotoxin Etoposide and Teniposidementioning

confidence: 99%

Antitumor Properties of Podophyllotoxin and Related Compounds

Gordaliza¹,

Ma²,

Jm³

et al. 2000

CPD

251

143

View full text Add to dashboard Cite

show abstract

“…Podophyllotoxin (1) is a natural bioactive plant-based lignan known to have significant antineoplastic and antiviral properties (Jardine, 1980;Bedows and Hatfield, 1982;Ayres and Loike, 1990;Bohlin and Rosen, 1996;Charlton, 1998;Canel et al, 2000;Gordaliza et al, 2001;Castro et al, 2003;Zhu et al, 2004). Its powerful cytotoxic properties have been attributed to its binding to tubulin during mitosis and thus inhibiting microtubule assembly (King and Sullivan, 1946;Desbène and Giorgi-Renault, 2001).…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…1. Except for their anti-tumour activities, podophyllotoxins possess insecticidal, phytotoxic and antiviral activities [11,12].…”

Section: Introductionmentioning

confidence: 99%

Production of 5-methoxypodophyllotoxin in cell suspension cultures of Linum flavum L.

Uden

Pras

Vossebeld

et al. 1990

Plant Cell Tiss Organ Cult

View full text Add to dashboard Cite

Cell suspension cultures of Linum flavum L., routinely grown on a NAA-containing medium, accumulated low levels of the phenylpropanoid-derived lignan 5-methoxypodophyllotoxin (5-MPT), up to 0.004% on a dry weight basis. Feeding experiments with the precursor L-phenylalanine resulted in a 3-5-fold increase in 5-MPT levels, but caused the levels of PAL activity to fall. Treatment of the cultures with the elicitor Nigeran, either alone or in combination with phenylalanine, caused the 5-MPT production to cease, even though PAL activity was rapidly enhanced by these treatments. Transfer of the cultures to NAA-free medium resulted in a 40-50 fold higher level of 5-MPT accumulation, the PAL activity levels being lowered compared to the routinely grown cells. With these more differentiated cultures, phenylalanine feeding and elicitor treatment, both on its own and in combination with the precursor, had no effect on 5-MPT production, even though the PAL activity levels were higher than in the untreated cells. It can be concluded that in lignan-accumulating cultures of L.flavum, PAL activity is nearly always detectable and seems to show a reciprocal relationship with 5-MPT accumulation.

show abstract

An Investigation of the Antiviral Activity of Podophyllum peltatum

Cited by 81 publications

References 9 publications

Antitumor Properties of Podophyllotoxin and Related Compounds

Antitumor Properties of Podophyllotoxin and Related Compounds

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

Production of 5-methoxypodophyllotoxin in cell suspension cultures of Linum flavum L.

Contact Info

Product

Resources

About