3590-93-0

Usage

Uses

Used in Pharmaceutical Industry:
4'-Demethyldeoxypodophyllotoxin is used as an active pharmaceutical ingredient for its inhibitory activity against human immunodeficiency virus reverse transcriptase and glycohydrolase, making it a potential candidate for the development of antiviral drugs, particularly for the treatment of HIV.
Used in Research and Development:
In the field of research and development, 4'-Demethyldeoxypodophyllotoxin is utilized as a key compound for studying its potential applications in medicine, including the development of new drugs targeting viral infections and other related diseases.
Used in Drug Synthesis:
4'-Demethyldeoxypodophyllotoxin serves as a starting material or intermediate in the synthesis of various pharmaceutical compounds, particularly those with antiviral properties, contributing to the advancement of drug discovery and innovation in the medical field.

Upstream product

• 477-51-0 deoxypodophyllotoxin 
• 40505-27-9 4-demethylpodophyllotoxin 
• 6559-91-7 4'-demethylepipodophyllotoxin 
• 518-28-5 podofilox 
• 96548-65-1 3-(benzo[d][1,3]dioxol-5-ylmethyl)-4-methoxy-4-oxobutanoic acid 
• 104485-87-2 (R)-(+)-α-(methylenedioxy-3,4 benzyl)hemisuccinate de methyle 
• 17187-77-8 (R)-(+)-3-piperonyl-4-butanolide 
• 123287-52-5 <(dimethoxy-3,5 hydroxy-4 phenyl)hydroxymethyl>-2 (methylenedioxy-3,4 benzyl)-3 butanolide-4 
• 70381-90-7 (S)-(-)-α-(methylenedioxy-3,4 benzyl)hemisuccinate de methyle 
• 70148-37-7 (S)-(-)-4-(3,4-methylenedioxybenzyl)dihydrofuran-2(3H)-one 
• 123287-52-5 <(dimethoxy-3,5 hydroxy-4 phenyl)hydroxymethyl>-2 (methylenedioxy-3,4 benzyl)-3 butanolide-4 
• 199464-34-1 C₂₂H₂₀O₇ 

Downstream Products

• 111142-77-9 Acetylderivat des 4-Desmethyl-7'-dehydroxy-podophyllotoxins 
• 13091-61-7 Ethyl-carbamic acid 2,6-dimethoxy-4-((5R,5aR,8aR)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester 
• 581799-49-7 4'-demethyl-9-deoxypodophyllol 

Relevant academic research and scientific papers

Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents

A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent.

Design, synthesis and biological evaluation of 4′-demethyl-4-deoxypodophyllotoxin derivatives as novel tubulin and histone deacetylase dual inhibitors

A new class of 4′-demethyl-4-deoxypodophyllotoxin derivatives has been designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluation of these hybrids included the inhibitory activity of HDAC, in vitro cell cycle analysis in HCT-116 cells as well as cytotoxicity against two cancer cell lines (A549 and HCT116). The distance and angle between the HDAC capping group and the zinc binding group were systematically varied. Compounds 14a and 14c showed most potent dual inhibitory activity and powerful antiproliferative activity on HCT116 and A549 cell lines. This journal is

Synthesis and biological evaluation of derivatives of 4- deoxypodophyllotoxin as antitumor agents

In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p- nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC50 values were 0.102, 0.180 and 0.0195 μM, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells.

Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects

In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4′-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4′-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4′- demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.

Natural products-based insecticidal agents 5. Design, semisynthesis and insecticidal activity of novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin against Mythimna separata Walker in vivo

In an attempt to find the effective phytopesticides, eight novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin were synthesized and preliminarily tested against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Among all of the tested analogs, compounds 5a, 5c, 5d, and 5h showed the higher insecticidal activity than 4-deoxypodophyllotoxin. Especially 5a exhibited the most potent insecticidal activity compared with toosendanin, a commercial insecticide derived from Melia azedarach.

First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin

Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.

Semisynthesis and quantitative structure-activity relationship (QSAR) study of novel aromatic esters of 4-demethyl-4-deoxypodophyllotoxin as lnsecticidal agents

By using podophyllotoxin as a phytoinsecticidal lead compound, 15 novel aromatic esters of 4'demethyl-4-deoxypodophyllotoxin were semisynthesized and preliminarily tested for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo for the first time. Among all of the tested compounds, especially two compounds, 4m and 4o, containing a pyridinyl group, for which final corrected mortality rates against M. separata at 1 mg/mL were 62.9 and 59.2%, respectively, showed the most promising and pronounced insecticidal activity as compared with toosendanin, a commercial insecticide derived from Melia azedarach. The quantitative structure-activity relationships (QSAR) of compounds 4a-4o showed that the relative number of benzene rings and final heat of formation were very important descriptors to their insecticidal activity.

Alkyl and carboxylalkyl esters of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxic, and antitumor activity

Esters of 4′-demethyl-4-deoxypodophyllotoxin (DDPT) with alkanoic acids and alkanedioic acids were prepared and tested for cytotoxic and antitumor activity. Among 19 esters, esters of propanoic acid, tetradecanedioic acid, 13-carboxyundecanoic acid, and h

Modes of methyleneoxy bridging and their effect on tetrahydronaphthalene lignan cytotoxicity

Dioxatricyclodecane, oxabicyclooctane, and benzodihydropyran derivatives of α-conidendrin (ACON), podophyllotoxin (PT), and sikkimotoxin (SK) were prepared to learn which methyleneoxy bridging modes and arene and aryl substituents coincided with high cytotoxicity. PT-derived dioxatricyclodecane 14 showed in vitro activity at 10-8 M. SK analogue 12 was less active, and ACON analogue 11 was inactive at 10-4 M. In vivo intraperitoneal and subcutaneous activities of 14 were observed. In vitro cytotoxicities were higher for oxabicyclooctanes when hydroxymethyl group and methyleneoxy bridge were cis, as in deoxypicropodophyllin analog 20, rather than trans, as in PT analogue 5. Acetylation of the hydroxymethyl group of 20 lowered activities, whereas acetylation of 5 increased or lowered activities. Reduction of the hydroxymethyl group of 5 to a methyl group increased cytotoxicities. Molecular dynamics indicated the THN scaffold of benzodihydropyrans was conformationally mobile, but scaffolds of oxabicyclooctanes and dioxatricyclodecanes were immobile. Each of three PT-benzodihydropyrans was less active than its oxabicyclooctane counterpart.