Syntheses and antitumor activity of cis-restricted combretastatins: 5-Membered heterocyclic analogues

Ohsumi, Koji; Hatanaka, Tsubasa; Fujita, Köichi; Nakagawa, Ryusuke; Fukuda, Youichi; Nihei, Yukio; Suga, Yasuhiro; Morinaga, Yasushi; Akiyama, Yukio; Tsuji, Takashi

doi:10.1016/s0960-894x(98)00579-4

Cited by 185 publications

(126 citation statements)

References 14 publications

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“…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%

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%

Tubulin-interactive stilbene derivatives as anticancer agents

Mikstacka

Stefański

Różański

2013

Cellular and Molecular Biology Letters

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“…The cis configuration only of 2a is biologically activity, with the trans form showing little or no activity 22 . The active cis double bond in 2a is readily converted to the more stable trans isomer during storage or metabolism, resulting in a dramatic decrease in antitumour activity 23 , 24 .…”

Section: Introductionmentioning

confidence: 99%

“…aroylindole 27 , 27 imidazole 30 , 1,3-dioxolane 31 , pyrazole 23 , furazan (1,2,5-oxadiazole) 25 and benzoxepin 32 ring systems. Such non-isomerisable compounds inhibit cell growth of several human cancer cell lines and many have been shown significant tubulin binding and depolymerising effects.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents

et al. 2010

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“…Therefore, non-isomerisable CA-4 analogues have been developed to provide more stable alternatives to CA-4. Approaches to prevent isomerisation have included the replacement of the cis-double bond in CA-4 with heterocyclic rings such as tetrazole, imidazole and benzoxepin (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%