Design, synthesis, biological evaluation and QSAR studies of novel bisepipodophyllotoxins as cytotoxic agents

Kamal, Ähmed; Laxman, E.; Khanna, Garima; Reddy, Post Sai; Rehana, Tasneem; Arifuddin, Mohammed; Khairatkar-Joshi, Neelima; Kondapi, Anand K.; Dastidar, Sunanda G.

doi:10.1016/j.bmc.2004.05.026

Cited by 26 publications

(7 citation statements)

References 28 publications

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“…Most of these analogs exhibited promising in vitro anticancer activity against different human tumor cell lines, and interestingly, 4'-O-methylated analogs showed superior topo II poisoning activity to etoposide. Especially, dimer (51) linked through the biphenyl spacer was the most active one of all tested compounds, the GI 50 values of which for DU145, HT29, and MCF7 were 0.2, 0.2 and 0.6, respectively [43].…”

Section: C-ring Modifications and Sarmentioning

confidence: 99%

A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003- 2007

徐¹,

Lv²,

Tian³

2009

CMC

185

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Podophyllotoxin is an important and much sought after antimitotic natural lead compound, since it paved the way for three hemisynthetic derivatives of podophyllotoxin, e.g., etoposide, teniposide and etopophos, which are widely used as anticancer drugs and show good clinical effects against several types of neoplasms. Although the publication of the recent reviews by Gordaliza in 2004 and You in 2005, which covered the literatures concerning podophyllotoxin until the early part of 2003, there have been significant number of works carried out on podophyllotoxin recently. Therefore, this review presents up-to-date coverage of podophyllotoxin in regard to hemisynthesis, biosynthesis, biological activities, mode of action and structure-activity relationship.

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Section: C-ring Modifications and Sarmentioning

confidence: 99%

A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003- 2007

徐¹,

Lv²,

Tian³

2009

CMC

185

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“…Current interest in dimeric analogs of lipophilic, neutral, DNA mono‐intercalating agents as potential antitumor drugs prompted Kamal et al . to prepare bis‐4β‐amino‐PPT dimers by linking the amino groups through various aryl spacers ( 405–418 ; Fig.…”

Section: Hemisynthesis and Structure–activity Relationshipsmentioning

confidence: 99%

Recent Progress on C‐4‐Modified Podophyllotoxin Analogs as Potent Antitumor Agents

Liu

Tian

Qian

et al. 2014

Medicinal Research Reviews

105

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Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, etoposide, teniposide, and the water-soluble prodrug etoposide phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C-4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure–activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL-331, TOP-53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new etoposide-related drugs and provides detailed coverage of the current status and recent development of C-4-modified PPT analogs as anticancer clinical trial candidates.

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“…Also the methyl group on the 4'-position of the pendent ring has little effect on the cytotoxicity. QSAR studies on epipodophyllotoxin dimers indicate that GI (50) activity is strongly dependent on structural and thermodynamic properties [10]. QSAR models for 157 epipodophyllotoxins have been reported using multiple topological descriptors of chemical structures, including molecular connectivity indices (MCI) and molecular operating environment descriptors [11].…”

Section: Fig 1 Structure Of Podophylotoxinmentioning

confidence: 99%

“…The topology descriptor has been used for developing QSAR for predicting the activity of small organic molecules towards Fusarium Rosium and Aspergillus niger [25]. Structural, thermodynamic and molecular operating environment descriptors have been reported by researchers developing QSAR for podophyllotoxin compounds [5,10]. LUMO (energy of the lowest unoccupied molecular orbital) as a descriptor in the QSAR equation has been reported for Aspergillus nidulans treated with chlorinated aliphatic hydrocarbons [20].…”

Section: Qsar Studiesmentioning

confidence: 99%

Synthesis, anti-fungal activity evaluation and QSAR studies on podophyllotoxin derivatives

et al. 2007

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Abstract:The anti-fungal and cytotoxic activites of podophyllotoxin and seven C-4 substituted podophyllotoxin ester derivatives, viz: trans-cinnamyl, cis-cinnamyl, o-methoxy cinnamyl, dimethyl acrylyl, p-methoxy phenyl acetyl, 3,4-dimethoxy phenyl acetyl and 2,5-dimethoxy phenyl acetyl esters were evaluated on four fungi, viz: Macrophomina phaseolina, Fusarium oxysporum, Myrrothecium verrucarria and Asperigillus candidus, The podophyllotoxin derivatives were synthesised and their structures were elucidated. Quantitative structure activity relationships were developed between the activity of these compounds against the four fungi and molecular descriptors. The linear regression models developed had one to two descriptors. For all the cases the r 2 was in the range of 0.73 to 0.96, indicating good data fit and q 2 was in the range of 0.60 to 0.68, indicating that the predictive capabilities of the models were acceptable. Solvent accessible surface area (namely the partial positive solvent-accessible surface area), A log P , highest occupied molecular orbital and conformational energy were identified as important descriptors.

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Design, synthesis, biological evaluation and QSAR studies of novel bisepipodophyllotoxins as cytotoxic agents

Cited by 26 publications

References 28 publications

A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003- 2007

A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003- 2007

Recent Progress on C‐4‐Modified Podophyllotoxin Analogs as Potent Antitumor Agents

Synthesis, anti-fungal activity evaluation and QSAR studies on podophyllotoxin derivatives

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