Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents.

Terada, T.; Fujimoto, Kohei; Nomura, Makoto; Yamashita, Jun‐ichi; Kobunai, Takashi; Takeda, Setsuo; Wierzba, Konstanty; Yamada, Yuji; Yamaguchi, Hideo

doi:10.1248/cpb.40.2720

Cited by 34 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[22] In the case of 2, the first intermediate formed was the benzylic carbocation generated at the 4-position under acidic medium (Lewis acid), in agreement to Kuhn and Von Wartburg. [23] This species is not stable enough during the demethylation process involving methanesulfonic acid and methionine.…”

Section: Introductionsupporting

confidence: 60%

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

Guminski

Grousseaud

Cugnasse

et al. 2012

Synthetic Communications

View full text Add to dashboard Cite

show abstract

Section: Introductionsupporting

confidence: 60%

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

Guminski

Grousseaud

Cugnasse

et al. 2012

Synthetic Communications

View full text Add to dashboard Cite

show abstract

“…6). All 4β-amido-2-substituted benzophenone analogues (35)(36)(37)(38)(39)(40) showed moderate cytotoxicity against all tested cell lines. Among 4β-sulphonamido aryl substituted derivatives, 41 is highly cytotoxic but the corresponding 4'-demethylated one (43) is less toxic by about 100-fold.…”

Section: Ring C Modificationsmentioning

confidence: 99%

“…4'-Demethyl-4-deoxypodophyllotoxin (DDPT) and 4-deoxypodophyllotoxin (DPT) have comparable potency in vitro [39]. However, in vivo experiments revealed a substantial loss of antitumor activity for DDPT in the solid tumor model, suggesting that the difference comes not from the cellular level, but from other aspects, and is possibly due to pharmacokinetic properties, such as absorption, metabolism, etc., or sites of action.…”

Section: Esters Carbonates and Carbamates Of Ddptmentioning

confidence: 99%

See 1 more Smart Citation

Podophyllotoxin Derivatives: Current Synthetic Approaches for New Anticancer Agents

You¹

2005

CPD

188

View full text Add to dashboard Cite

Podophyllotoxin is an antimitotic natural product. Its inhibitory activity on cell growth led to the development of the clinically valuable anticancer agents, etoposide, teniposide and the water-soluble prodrug, etoposide phosphate. The cytotoxic mechanism of these drugs is the inhibition of topoisomerase II, unlike the lead compound which inhibits mitosis. Through extensive structure-activity relationship studies, several potential drug candidates were synthesized such as GL-331, TOP 53, NK611, and azatoxin. Recently, more complex and diverse analogues have been synthesized either to get more potent compounds or to overcome drug resistance. At the same time, a number of prodrug approaches have been tried to enhance the tumor selectivity or to increase the aqueous solubility. The prodrugs can release cytotoxic etoposide through the actions of hydrolysis, enzymes or catalytic antibodies. More sophisticated prodrug strategies have been applied in etoposide and these produced some interesting results. In this review, the current research trends in the design of new derivatives will be covered with a brief introduction of podophyllotoxin and related analogues.

show abstract

“…Moreover, it was reported that 4′‐demethyl‐4‐deoxypodophyllotoxin ( 6 ) had a comparable in vitro potency respect to 4‐deoxypodophyllotoxin ( 5 ). However, the antitumor activity of 4′‐demethyl‐4‐deoxypodophyllotoxin ( 6 ) in the BDF1/3LL model was substantially less than that of 4‐deoxypodophyllotoxin ( 5 ) .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Cytotoxic Isodeoxypodophyllotoxin Analogs

Heidary

Emami

Dehghan

et al. 2016

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

A series of aryltetralin lignans 7a-l were synthesized as cytotoxic isodeoxypodophyllotoxin analogs. The title compounds 7a-l were synthesized from the reaction of (+)-(R)-4-[benzo(d)(1,3)dioxol-5-ylmethyl]dihydrofuran-2-(3H)-one with different arylaldehydes to afford benzyl alcohol analogs and subsequent cyclization with trifluoroacetic acid in dichromethane. The preliminary screening of the compounds against viability of blood cancer human cell line K562 revealed that compounds 7d, 7e, and 7f had higher inhibitory activity at 10 μg/mL concentration compared with etoposide as reference drug. J = 6.9 Hz, J = 13.7 Hz, H-6), 2.37 (dd, J = 8.7 Hz, J = 13.7 Hz, H-6), 2.47 (m, H-4), 2.92 (dd, J = 8.3 Hz, J = 9.3 Hz, H-3), 3.08 (dd, J = 5.0 Hz, J = 15.3 Hz, H-3), 3.17 (m, H-4), 3.74 (s, -OMe), 3.80 (s, -OMe), 3.91 (s, -OMe), 3.98 anti (m, J = 9.0 Hz, H-5), 4.13 syn (dd, J = 7.25Hz, J = 14.4 Hz, H-5), 4.46 anti (t, J = 8.0 Hz, H-5), 4.512 syn (m, H-7), 4.72 anti (d, J = 8.6 Hz, H-7), 5.09 syn (s, J = 5.6 Hz, H-7), 5.86 (s, 2H, OCH 2 O), 6.27-6.68 (m, 3H, aromatic H), 7.33 (d, 1H, J = 5.7 Hz, aromatic). FT-IR (film) ν max : 3460, (OH), 1770 (C=O) cm À1 . ESI-Mass m/z: 409 [M + Na] + . Anal. Calcd for C 21 H 22 O 7 : C, 67.41; H, 5.66. Found: C, 67.55; H, 5.72. (3S,4R)-4-[Benzo(d)(1,3)dioxol-5-ylmethyl]-3-[hydroxy(2,3dimethoxyphenyl)methyl]-dihydrofuran-2(3H)-one (9h). Yield 65% as a mixture of diasteromers (anti/syn: 50/50); 1 H

show abstract

Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents.

Cited by 34 publications

References 0 publications

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

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

Podophyllotoxin Derivatives: Current Synthetic Approaches for New Anticancer Agents

Synthesis of Cytotoxic Isodeoxypodophyllotoxin Analogs

Contact Info

Product

Resources

About