1,2,3-Triazole analogs of combretastatin A-4 as potential microtubule-binding agents

Odlo, Kristin; Fournier-Dit-Chabert, Jérémie; Ducki, Sylvie; Gani, Osman; Sylte, Ingebrigt; Hansen, Trond Vidar

doi:10.1016/j.bmc.2010.07.032

Cited by 80 publications

(42 citation statements)

References 60 publications

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“…The analogs, 1-(3,4,5-trimethoxyphenyl)-5-(2,3-diamino-4-methoxyphenyl)-1,2,3-triazole (Table 1, compound 15) and 1-(3,4,5-trimethoxyphenyl)-5-(3-amino-4-methoxyphenyl)-1,2,3-triazole (Table 1, compound 16) displayed an inhibitory effect on tubulin polymerization comparable to that of CA-1 with respective IC 50 of 5.2 µM and 4.5 µM versus 3.5 µM for CA-1 [82]. 1,4-disubstituted 1,2,3-triazole analogs of CA-4 were significantly less cytotoxic [85].…”

Section: Other Synthetic Stilbene Derivatives As Tubulin-interactive mentioning

confidence: 99%

“…The rationale of the design of active compounds was to retain the appropriate geometry of the two adjacent aryl groups required for potent bioactivity of chemically stable cis-restricted derivatives of CA-4. These were obtained by incorporating the olefinic double bond into vicinally diaryl-substituted fivemember aromatic heterocyclic rings (Table 1), such as pyrazole [67], imidazole [67][68][69], thiazole [70][71][72], furazan (1,2,5-oxadiazole) [73], furan [74,75], thiophene [76,77], isoxazole [78,79], oxazole [67,68,80,81], 1,2,3-thiadiazole [39], triazole [82,83,84,85], 1,2,3,4-tetrazole [70,86] and dioxolane [87]. Replacement of the olefinic bond with a five-member heterocyclic ring allowed the retention of the correct geometric orientation of the two phenyl rings of CA-4, placing them at an appropriate distance for efficient interaction with the colchicine-binding domain on tubulin [35].…”

Section: Other Synthetic Stilbene Derivatives As Tubulin-interactive mentioning

confidence: 99%

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Tubulin-interactive stilbene derivatives as anticancer agents

Mikstacka

Stefański

Różański

2013

Cellular and Molecular Biology Letters

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Microtubules are dynamic polymers that occur in eukaryotic cells and play important roles in cell division, motility, transport and signaling. They form during the process of polymerization of α- and β-tubulin dimers. Tubulin is a significant and heavily researched molecular target for anticancer drugs. Combretastatins are natural cis-stilbenes that exhibit cytotoxic properties in cultured cancer cells in vitro. Combretastatin A-4 (3′-hydroxy-3,4,4′, 5-tetramethoxy-cis-stilbene; CA-4) is a potent cytotoxic cis-stilbene that binds to β-tubulin at the colchicine-binding site and inhibits tubulin polymerization. The prodrug CA-4 phosphate is currently in clinical trials as a chemotherapeutic agent for cancer treatment. Numerous series of stilbene analogs have been studied in search of potent cytotoxic agents with the requisite tubulin-interactive properties. Microtubule-interfering agents include numerous CA-4 and transresveratrol analogs and other synthetic stilbene derivatives. Importantly, these agents are active in both tumor cells and immature endothelial cells of tumor blood vessels, where they inhibit the process of angiogenesis. Recently, computer-aided virtual screening was used to select potent tubulin-interactive compounds. This review covers the role of stilbene derivatives as a class of antitumor agents that act by targeting microtubule assembly dynamics. Additionally, we present the results of molecular modeling of their binding to specific sites on the α- and β-tubulin heterodimer. This has enabled the elucidation of the mechanism of stilbene cytotoxicity and is useful in the design of novel agents with improved anti-mitotic activity. Tubulin-interactive agents are believed to have the potential to play a significant role in the fight against cancer.

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Section: Other Synthetic Stilbene Derivatives As Tubulin-interactive mentioning

confidence: 99%

Section: Other Synthetic Stilbene Derivatives As Tubulin-interactive mentioning

confidence: 99%

Tubulin-interactive stilbene derivatives as anticancer agents

Mikstacka

Stefański

Różański

2013

Cellular and Molecular Biology Letters

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“…194 Both thermal and ruthenium-catalyzed conditions were examined, where the bicyclic triazole product 113 was produced in both higher yield and shorter reaction time using the Ru-catalyzed reaction (Scheme 53). [197][198] scaffolds. Tron and co-workers envisaged that the same two building blocks, i.e.…”

Section: Scheme 49mentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years. CONTENTS

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“…Preparation of azide 170 was achieved from the boronic acid 169 in reaction with copper sulphate and sodium azide as previously reported. 243 The azide was used without further purification after work up. For the synthesis of the dinitro compound 173, 4-methoxy-2-nitro-benzealdehyde (171) was treated with nitric acid in fuming sulphuric acid (Scheme 12).…”

Section: Synthesis and Biological Evaluation Of Combretastatin A-1 Anmentioning

confidence: 99%