- Study of 5-azidomethyl-8-hydroxyquinoline structure by X-ray diffraction and HF–DFT computational methods
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5-Azidomethyl-8-hydroxyquinoline has been synthesized and characterized using IR, 1H and 13C NMR spectroscopic methods. Thermal analysis revealed no solid-solid phase transitions. The crystal structure of this compound was refined by Rietveld method from powder X-ray diffraction data at 295 K. The single- crystal structure of the compound at 260 K was solved and refined using SHELX 97 program. According to the data obtained by both methods, the structure of the compound is monoclinic, space group P21/c, with Z = 4 and Z' = 1. For the single crystal at 260 K, a = 12.2879 (9) ?, b = 4.8782 (3) ?, c = 15.7423 (12) ?, β=100.807(14)°. Mechanisms of deformation resulting from intra- and intermolecular interactions, such as hydrogen bonding, induced slight torsions in the crystal structure. The optimized molecular geometry of 5-azidomethyl-8-hydroxyquinoline in the ground state is calculated using density functional theory (B3LYP) and Hartree-Fock (HF) methods with the 6-311G(d,p) basis set. The calculated results show good agreement with experimental values. Energy gap of the molecule was found using HOMO and LUMO calculation which reveals that charge transfer occurs within the molecule.
- Bougharraf,Benallal,Sahdane,Mondieig,Negrier, Ph.,Massip,Elfaydy,Lakhrissi,Kabouchi
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- Synthesis and biological evaluation of indole-based UC-112 analogs as potent and selective survivin inhibitors
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The anti-apoptotic protein survivin is highly expressed in cancer cells but has a very low expression in fully differentiated adult cells. Overexpression of survivin is positively correlated with cancer cell resistance to chemotherapy and radiotherapy, cancer cell metastasis, and poor patient prognosis. Therefore, selective targeting survivin represents an attractive strategy for the development of anticancer therapeutics. Herein, we reported the extensive structural modification of our recently discovered selective survivin inhibitor UC-112 and the synthesis of thirty-three new analogs. The structure-activity relationship (SAR) study indicated that replacement of the benzyloxy moeity in UC-112 with an indole moiety was preferred to other moieties. Among these UC-112 analogs, 10f, 10h, 10k, 10n showed the most potent antiproliferative activities. Interestingly, they were more potent against the P-glycoprotein overexpressing cancer cell lines compared with the parental cancer cell lines. Mechanistic studies confirmed that new analogs maintained their unique selectivity against survivin among the IAP family members. In vivo study using 10f in a human A375 melanoma xenograft model revealed that it effectively inhibited melanoma tumor growth without observable acute toxicity. Collectively, this study strongly supports the further preclinical development of selective survivin inhibitors based on the UC-112 scaffold.
- Wang, Qinghui,Arnst, Kinsie E.,Xue, Yi,Lei, Zi-Ning,Ma, Dejian,Chen, Zhe-Sheng,Miller, Duane D.,Li, Wei
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- Synthesis of novel 5,7-disubstituted 8-hydroxyquinolines
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(Chemical Equation Presented) Seven new 5,7-disubstituted oxine derivatives have been synthesized via a Mannich reaction between a sec. amine (e.g. piperidine, pyrrolidine, morpholine, or dibenzylamine,) and 5-cyano or 5-azidomethyl-8-hydroxyquinoline, which were respectively obtained by nucleophilic displacement of 5-chloromethyl-8-hydroxyquinoline by cyanide or azide anions. In all cases, a single product was isolated in medium to fair yield and characterized on the basis of 1H and 13C-NMR, MS and IR spectrometric data. The X-ray structure of the product obtained from 5-cyanomethyl-8-hydroxyquinoline and piperidine is also reported.
- Himmi, Banacer,Joly, Jean-Pierre,Hlimi, Fouzia,Soufiaoui, Mohamed,Kitane, Said,Bahloul, Abdelmejid,Eddaif, Abdelhamid,Sebban, Abdelfatah
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p. 1023 - 1026
(2008/12/20)
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