- Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors
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A series of 7-substituted coumarins incorporating various glycosyl moieties were synthesized and investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the housekeeping, offtarget isoforms CA I and II, but some of them inhibited tumor-associated CA IX and XII in the low nanomolar range. They also significantly inhibited the growth of primary tumors by the highly aggressive 4T1 syngeneic mouse mammary tumor cells at 30 mg/kg, constituting interesting candidates for the development of conceptually novel anticancer drugs. Because CA IX is overexpressed in hypoxic tumors and exhibits very limited expression in normal tissues, such compounds may be useful for treating cancers not responsive to classic chemo- and radiotherapy.
- Touisni, Nadia,Maresca, Alfonso,McDonald, Paul C.,Lou, Yuanmei,Scozzafava, Andrea,Dedhar, Shoukat,Winum, Jean-Yves,Supuran, Claudiu T.
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- Synthesis and Properties of Alkoxyethyl β-d-Xylopyranoside
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In order to improve the water solubility of sugar-based surfactants, alkyl β-d-xylopyranosides, novel sugar-based surfactants, 1,2-trans alkoxyethyl β-d-xylopyranosides, with alkyl chain length n = 6–12 were stereoselectively prepared by the trichloroacetimidate method. Their properties including hydrophilic–lipophilic balance (HLB) number, water solubility, surface tension, emulsification, foamability, thermotropic liquid crystal, and hygroscopicity were investigated. The results indicated that their HLB number decreased with increase of alkyl chain, the water solubility improved since the hydrophilic oxyethene (─OCH2CH2─) fragment was introduced. The dissolution process was entropy driven at 25–45 °C for alkyl chain length n = 6–10. Octyloxyethyl β-d-xylopyranoside had the best foaming ability. Nonyloxyethyl β-d-xylopyranoside had the best foam stability and the emulsifying ability was better in toluene/water system than in rapeseed oil/water system. The surface tension of in aqueous solution dropped to 27.8 mN m?1 at the critical micelle concentration, and it also showed the most distinct thermotropic liquid phases with cross pattern texture upon heating and the fan schlieren texture on cooling. Hexyloxyethyl β-d-xylopyranoside possessed the strongest hygroscopicity. Based on the effective improvement of water solubility, the prepared alkoxyethyl β-d-xylopyranosides showed excellent surface activity and are expected to develop their practical application as a class of novel sugar-based surfactants.
- Shen, Wangzhen,Ji, Shanwei,Chen, Langqiu,Zhang, Yanhua,Wu, Xiubing
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- Novel xylosidesurfactant
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The invention belongs to the technical field of surfactants for fine chemistry and discloses a novel sugar-based surfactant, namely, alkoxyethyl-beta-D-xylopyranoside in order to solve the problem of limitation to application of traditional alkyl glycoside as the surfactant due to the fact water solubility of traditional alkyl glycoside is gradually reduced with increase of carbon chain length. Compared with traditional alkyl glycoside with the same carbon chain length, the surfactant has better water solubility and surface activity as well as selectable and controllable foaming capacity and emulsifying property. Besides, raw materials for synthesis comprisexylose obtained from waste crop leftovers and naturally-sourced fatty alcohol and have rich sources. The glycoside can be widely applied to application industries such as biochemical engineering, pharmacy, pesticides, food processing, cosmetics, scientific research and the like.
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- Natural product-like combinatorial libraries based on privileged structures. 1. General principles and solid-phase synthesis of benzopyrans
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Herein we report a novel strategy for the design and construction of natural and natural product-like libraries based on the principle of privileged structures, a term originally introduced to describe structural motifs capable of interacting with a variety of unrelated molecular targets. The identification of such privileged structures in natural products is discussed, and subsequently the 2,2-dimethylbenzopyran moiety is selected as an inaugural template for the construction of natural product-like libraries via this strategy. Initially, a novel solid-phase synthesis of the benzopyran motif is developed employing a unique cycloloading strategy that relies on the use of a new, polystyrene-based selenenyl bromide resin. Once the loading, elaboration, and cleavage of these benzopyrans was established, this new solid-phase method was then thoroughly validated through the construction of six focused combinatorial libraries designed around natural and designed molecules of recent biological interest.
- Nicolaou,Pfefferkorn,Roecker,Cao,Barluenga,Mitchell
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p. 9939 - 9953
(2007/10/03)
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- Synthesis of XylβCer, Galβ1-4XylβCer, NeuAcα2-3Galβ1-4XylβCer and the Corresponding Lactone and Lactam Trisaccharides
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2-(Trimethylsilyl)ethyl 2-O-benzoyl- and 2,3-di-O-acetyl-β-D-xylopyranosides (12 and 14) were synthesized in high yields and subjected to glycosylation with various glycosyl donors. Galactosylation of 12 gave the xylose analogue of TMSEt lactoside (3), which was transformed into the glycosyl acceptor 19. Sialylation then gave the xylose analogue of GM3 trisaccharide (5). The TMSEt glycosides 10, 25, and 32 were transformed into the corresponding trichloroacetimidates, which were used for glycosylation of an azidosphingosine derivative. The resulting sphingosyl glycosides were transformed into the title ceramides. Treatment of NeuAcα2-3Galβ1-4XylβCer (5) with acetic acid gave the corresponding 1″→2′-lactone 7. Glycosylation of 12 or 14 with a GM4-lactam donor (40) gave the xylose analogue of GM3-lactam (42). There was a 3-fold increase in the formation of GAG chains in the presence of 0.5 μM XylβCer (2) in the medium.
- Wilstermann, Michael,Magnusson, Goeran
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p. 7961 - 7971
(2007/10/03)
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