Synthesis of 10-substituted triazolyl artemisinins possessing anticancer activity via Huisgen 1,3-dipolar cylcoaddition

Cho, Sungsik; Oh, Sangtae; Um, Yumi; Jung, Jihee; Ham, Jungyeob; Shin, Woon‐Seob; Lee, Seokjoon

doi:10.1016/j.bmcl.2008.11.067

Cited by 51 publications

(9 citation statements)

References 24 publications

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“…Antitumor activity of deoxoartemisinin dimers has also been studied by Jeyadevan et al [106] and Posner et al [107]. Cho et al [108] synthesized 10-substitured triazolylartemisinin compounds and tested them on various cancer cell lines (human colorectal adenocarcinoma, human glioma, human cervical carcinoma and mouse melanoma). The GI 50 s of most of these compounds were less than 1 μM.…”

Section: Other Monomers and Artemisinin Hybridsmentioning

confidence: 97%

Development of artemisinin compounds for cancer treatment

2012

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Artemisinin contains an endoperoxide moiety that can react with iron to form cytotoxic free radicals. Cancer cells contain significantly more intracellular free iron than normal cells and it has been shown that artemisinin and its analogs selectively cause apoptosis in many cancer cell lines. In addition, artemisinin compounds have been shown to have anti-angiogenic, anti-inflammatory, anti-metastasis, and growth inhibition effects. These properties make artemisinin compounds attractive cancer chemotherapeutic drug candidates. However, simple artemisinin analogs are less potent than traditional cancer chemotherapeutic agents and have short plasma half-lives, and would require high dosage and frequent administration to be effective for cancer treatment. More potent and target-selective artemisinin-compounds are being developed. These include artemisinin dimers and trimers, artemisinin hybrid compounds, and tagging of artemisinin compounds to molecules that are involved in the intracellular iron-delivery mechanism. These compounds are promising potent anticancer compounds that produce significantly less side effect than traditional chemotherapeutic agents.

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Section: Other Monomers and Artemisinin Hybridsmentioning

confidence: 97%

Development of artemisinin compounds for cancer treatment

2012

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“…As a consequence of this awareness, increased research efforts are focused on new derivatives with innovative applications and improved properties. Major pharmaceutical companies are beginning to take an interest in developing new trioxane compounds [18] , [19] , [20] , [21] .…”

Section: Introductionmentioning

confidence: 99%

LC–UV/MS quality analytics of paediatric artemether formulations

Vandercruyssen

D׳Hondt

Vergote

et al. 2014

Journal of Pharmaceutical Analysis

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A highly selective and stability-indicating HPLC-method, combined with appropriate sample preparation steps, is developed for β-artemether assay and profiling of related impurities, including possible degradants, in a complex powder for oral suspension. Following HPLC conditions allowed the required selectivity: a Prevail organic acid (OA) column (250 mm×4.6 mm, 5 μm), flow rate set at 1.5 mL/min combined with a linear gradient (where A=25 mM phosphate buffer (pH 2.5), and B=acetonitrile) from 30% to 75% B in a runtime of 60 min. Quantitative UV-detection was performed at 210 nm. Acetonitrile was applied as extraction solvent for sample preparation. Using acetonitrile–water mixtures as extraction solvent, a compartmental behaviour by a non-solving excipient-bound fraction and an artemether-solubilising free fraction of solvent was demonstrated, making a mobile phase based extraction not a good choice. Method validation showed that the developed HPLC-method is considered to be suitable for its intended regulatory stability-quality characterisation of β-artemether paediatric formulations. Furthermore, LC–MS on references as well as on stability samples was performed allowing identity confirmation of the β-artemether related impurities. MS-fragmentation scheme of β-artemether and its related substances is proposed, explaining the m/z values of the in-source fragments obtained.

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“…The organic layer (ethyl acetate) was dried (Na 2 SO 4 ) and concentrated in vacuo to furnish the crude products. Pure DHA monomers and dimers(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) were obtained by column chromatography (silica gel) using hexane-ethyl acetate (8-5:2-5 v/v) as eluent.3-[4'-{1a'-(12aβ-Dihydroxyartemisinoxy)}-ethoxyphenyl]-1-(2", 4"-dimethoxyphenyl)-2-propen-1-one (6): Elution of the column with n-hexane-ethyl acetate (70:20) yielded a viscous compound, 90% (w/w) yield; IR ν max (neat): 1654 (chalcone), 1253, 1169, 1109 (ether), 1601, 1459, 1362, 1026, 984 (aromatics) cm -1 ; 1 H, COSY-NMR (300 MHz, Acetone-d 6 ): δ 0.84 (3H, d, J =9.3 Hz, H 3 -13a), 0.88 (3H, d, J =7.5 Hz, H 3 -14a), 1.21 (3H, s, H 3 -15a), 2.46 (1H, m, H-11a), 3.88, 3.95 (3H each, s, 2 x OCH 3 ), 3.79 (1H, m, Ha-1a'), 4.05 (1H, m, Hb-1a'), 4.27 (2H, d, J=6.3 Hz, H 2 -2a'), 4.78 (1H, d, J=3.0 Hz, αH-12a), 5.42 (1H, s, H-5a), 6.60 (1H, d, J = 2.4 Hz, H-3"), 6.64 (1H, dd, J = 8.7, 2.1 Hz, H-5"), 7.02 (2H, dd, J= 8.7, 1.8 Hz, H-3', H-5'), 7.48 (1H, d, J= 15.9 Hz, H-2), 7.58 (1H, d, J= 15.9 Hz, H-3), 7.64 (1H, m, H-6"), 7.66 (2H, d, J= 8.7 Hz, H-2', H-6'); 13 C, DEPT-NMR (75 MHz, Acetone-d 6 ): δ 12.82 (C-13a), 20.18 (C-14a), 24.64 (C-8a), 25.07 (C-2a), 25.75 (C-15a), 31.29 (C-11a), 34.96 (C-9a), 36.68 (C-3a), 37.57 (C-10a), 44.90 (C-7a), 53.00 (C-1a), 55.51, 55.79 (2 x OCH 3 ), 66.54 (C-1a'), 67.92 (C-2a'), 81.01 (C-6a, q), 87.91 (C-5a), 98.79 (C-3"), 101.99 (C12a), 103.88 (C-4a, q), 106.13 (C-5"), 115.54 (C-5', C-5'), 122.73 (C-1", q), 125.58 (C-2), 128.60 (C-1', q), 130.34 (C-2', C-6'), 132.68 (C-6"), 141.33 (C-3), 160.89 (C-2", q), 161.17…”

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confidence: 99%