Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates

O’Boyle, Niamh M.; Ana, Gloria; Kelly, P.M.; Nathwani, Seema M.; Noorani, Sara; Fayne, Darren; Bright, Sandra A.; Twamley, Brendan; Zisterer, Daniela M.; Meegan, Mary J.

doi:10.1039/c9ob00558g

Cited by 18 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All synthesized analogs were tested against MCF-7 cells. Two amino-containing derivatives 4q, 4x and hydroxyl derivative 4m exhibited strong activity with 130 nM, 83 nM and 190 nM IC 50 values, respectively [68].…”

Section: Antiproliferative Activitymentioning

confidence: 98%

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

et al. 2020

View full text Add to dashboard Cite

Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.

show abstract

Section: Antiproliferative Activitymentioning

confidence: 98%

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Derivative 43 revealed an IC 50 value of 83 nM against MCF-7 breast cancer cells, unfortunately, the activity of 43 is not as high as the lead compound combretastatin-A4 (IC 50 ¼ 3.9 nM). Furthermore, compound 43 was selectively toxic to MCF cells, inducing G2/M phase arrest and apoptosis of MCF-7 cells, but not in peripheral blood monocytes, and inducing cleavage of DNA repair enzyme poly adenosine diphosphate ribose polymerase (PARP) in MCF-7 cells 68 . Singh et al reported the synthesis and anticancer activities of colchicine derivatives.…”

Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Piperazine moiety is a cyclic molecule containing two nitrogen atoms in positions 1 and 4, as well as four carbon atoms. Piperazine is one of the most sought heterocyclics for the development of new drug candidates with a wide range of applications. Over 100 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antioxidant, and other activities, were reviewed. This article reviewed investigations regarding piperazine groups for the modification of natural product derivatives in the last decade, highlighting parameters that affect their biological activity.

show abstract

“…Docking studies indicate that the trimethoxy A rings overlay with with those of DAMA-colchicine, whilst the B ring of the piperazine conjugates align with the the C ring of DAMA-colchicine. Toxicity of the compounds is minimal and water-soluble conjugates will be developed for the potential treatment of triple-negative breast cancer [101].…”

Section: Piperazine Conjugatesmentioning

confidence: 99%

Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

2020

Self Cite

View full text Add to dashboard Cite

It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.

show abstract

Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates

Abstract: We report novel cis-restricted combretastatin A-4 analogues with potent antiproliferative effects in breast cancer cells.

Cited by 18 publications

References 34 publications

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Piperazine skeleton in the structural modification of natural products: a review

Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

Contact Info

Product

Resources

About