Synthesis of combretastatin A-4 O-alkyl derivatives and evaluation of their cytotoxic, antiangiogenic and antitelomerase activity

Torijano-Gutiérrez, Sandra; Díaz‐Oltra, Santiago; Falomir, Eva; Murga, Juan; Cardá, Miguel; Marco, J. Alberto

doi:10.1016/j.bmc.2013.09.064

Cited by 15 publications

(7 citation statements)

References 73 publications

(4 reference statements)

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“…Unless otherwise noted, the reagents were purchased from commercial sources and were used directly without further purification. Substrates 1q , 1r , 1s , and 1t were prepared according to the literature procedures.…”

Section: Methodsmentioning

confidence: 99%

Copper-Catalyzed Asymmetric Borylacylation of Styrene and Indene Derivatives

Yang

Lü

et al. 2021

J. Org. Chem.

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The enantioselective copper-catalyzed borylacylation of aryl olefins with acyl chlorides and bis-(pinacolato)diboron is reported. This three-component reaction involves an enantioselective syn-borylcupration of the aryl olefin, followed by a nucleophilic attack on the acyl chloride. This reaction proceeds with a 2 mol % catalyst loading and is generally completed within 30 min at room temperature. Because the boron moiety can be converted into versatile functional groups and the carbonyl group is a ubiquitous functional group, the resulting chiral β-borylated ketones are versatile intermediates in organic synthesis.

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Section: Methodsmentioning

confidence: 99%

Copper-Catalyzed Asymmetric Borylacylation of Styrene and Indene Derivatives

Yang

Lü

et al. 2021

J. Org. Chem.

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“…New MTAs of natural or synthetic origin are still to be discovered and tested in (pre-) clinical investigation. Combretastatin and its analogs (such as Ombrabulin, first isolated from Combretum caffeum ) demonstrated potent antitumor activity and safety in the treatment of ovarian cancer [ 121 , 122 , 123 , 124 ]. Epothilones belong to the microtubule-stabilizing group of MTAs, being first discovered as antifungal agents produced by Sorangium cellulolus ([ 125 ] and references therein).…”

Section: Addressing Inhibition Of Cell Division In Cancer Therapymentioning

confidence: 99%

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Roth

Gihring

Bischof

et al. 2022

Cancers

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Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. Additionally, site-specific phosphorylation of microtubule-associated proteins can be related to the maintenance of genomic stability but also microtubule stabilization/destabilization, e.g., by hyper-phosphorylation of microtubule-associated protein 1A and RITA1. Consequently, approaches interfering with Casein Kinase 1-mediated microtubule-specific functions might be exploited as therapeutic strategies for the treatment of cancer. Currently pursued strategies include the development of Casein Kinase 1 isoform-specific small molecule inhibitors and therapeutically useful peptides specifically inhibiting kinase-substrate interactions.

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“…During the past few years, we have been investigating a range of analogues of natural products for their potential values in anticancer therapy as multitarget agents [22,23]. We have published several reports on the biological properties of combretastatin and aminocombretastatin A-4 derivatives [24][25][26][27][28][29]. In addition to their cytotoxicity, we have also investigated their ability to inhibit the expression of certain genes related to the angiogenesis process and the telomerase activation, such as c-Myc, VEGF and hTERT genes, as well as their actions as vascular disrupting agents.…”

Section: Figurementioning

confidence: 99%

Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tubulin and as Downregulators of the VEGF, hTERT and c-Myc Gene Expression

et al. 2020

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Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3′-aminocombretastatin A-4 (AmCA-4) have shown promising antitumor activities. In this study, a range of CA-4 and AmCA-4 derivatives containing amino acid pendants have been synthesized in order to compare their biological actions with those of their parent compounds. Thus, inhibition of cell proliferation on tumor cell lines HT-29, MCF-7 and A-549, as well as on the nontumor cell line HEK-273; in vitro tubulin polymerization; mitotic cell arrest; action on the microtubule cell network and inhibition of VEGF, hTERT, and c-Myc genes have been evaluated. Some AmCA-4 derivatives bearing L-amino acids exhibited inhibition of cell proliferation at low nanomolar levels exceeding the values shown by AmCA-4. Furthermore, while CA-4 and AmCA-4 derivatives do not show significant effects on the in vitro tubulin polymerization and cell cycle arrest, some selected CA-4 and AmCA-4 derivatives are able to cause total depolymerization of the microtubule network on A-549 cells. The best results were obtained in the inhibition of gene expression, particularly on the VEGF gene, in which some AmCA-4 derivatives greatly exceeded the inhibition values achieved by the parent compound.

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Synthesis of combretastatin A-4 O-alkyl derivatives and evaluation of their cytotoxic, antiangiogenic and antitelomerase activity

Cited by 15 publications

References 73 publications

Copper-Catalyzed Asymmetric Borylacylation of Styrene and Indene Derivatives

Copper-Catalyzed Asymmetric Borylacylation of Styrene and Indene Derivatives

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tubulin and as Downregulators of the VEGF, hTERT and c-Myc Gene Expression

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