Acetyl analogs of combretastatin A-4: Synthesis and biological studies

Lee, Moses; Babu, Balaji; Lee, Megan; Lee, Lauren; Strobel, Raymond; Brockway, Olivia; Nickols, Alexis; Sjoholm, Robert; Tzou, Samuel; Chavda, Sameer; Desta, Dereje; Fraley, Gregory S.; Siegfried, Adam; Pennington, William T.; Hartley, Rachel; Westbrook, Cara; Mooberry, Susan L.; Kiakos, Konstantinos; Hartley, John A.

doi:10.1016/j.bmc.2011.02.018

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…Lee’s group (158,159) developed a series of acetylated ( 198 ) and methylpyrazoline ( 199 , Fig. 15) analogs of CA-4 with the intention to improve solubility of the CA-4 analogs.…”

Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs.

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“…Lee’s group (158,159) developed a series of acetylated ( 198 ) and methylpyrazoline ( 199 , Fig. 15) analogs of CA-4 with the intention to improve solubility of the CA-4 analogs.…”

Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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“…Specifically, the acetylated analogs of combretastatin were found to exhibit good cytotoxicity and microtubule depolymerization potency, making them worthy of further investigation [14]. One potential challenge for the acetylcombretastatins is their susceptibility to detoxification by biological nucleophiles such as glutathione [15].…”

Section: Introductionmentioning

confidence: 98%

“…The authors' laboratory has also developed a series of acetylated analogs of combretastatins [14]. Specifically, the acetylated analogs of combretastatin were found to exhibit good cytotoxicity and microtubule depolymerization potency, making them worthy of further investigation [14].…”

Section: Introductionmentioning

confidence: 98%

A novel class of trans-methylpyrazoline analogs of combretastatins: Synthesis and in-vitro biological testing

Lee

Brockway

Dandavati

et al. 2011

European Journal of Medicinal Chemistry

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“…1), a natural product isolated from the bark of the South African bush willow tree Combretum caffrum , [1, 2] possesses high cytotoxic activity against multiple human cancer cells, including multidrug resistant cancer cell lines [3, 4]. The molecule binds at or near the colchicine site and inhibits tubulin polymerization, and this ultimately leads to cell death [5].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues

Elagawany¹,

Schmitt²,

Ghiaty³

et al. 2013

ACAMC

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Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDA-MB-435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.

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Acetyl analogs of combretastatin A-4: Synthesis and biological studies

Cited by 12 publications

References 26 publications

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

A novel class of trans-methylpyrazoline analogs of combretastatins: Synthesis and in-vitro biological testing

Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues

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