- Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
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A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells. The target compounds were also evaluated for their inhibition activity of tubulin polymerization. Further, the treatment of compound 13d on DU145 cells led to the inhibition of cell migration ability. The detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 13d induced apoptosis in DU145 cells. The influence of the cytotoxic compound 13d on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, the treatment with compound 13d caused collapse of mitochondrial membrane potential and elevated intracellular ROS levels in DU145 cells. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Thus, this new molecular scaffold could be a new lead for the development of anticancer agents that target tubulin.
- Guggilapu, Sravanthi Devi,Guntuku, Lalita,Reddy, T. Srinivasa,Nagarsenkar, Atulya,Sigalapalli, Dilep Kumar,Naidu,Bhargava, Suresh K.,Bathini, Nagendra Babu
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- Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents
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A series of novel triazole derivatives containing γ-lactam were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR and HRMS. The in vitro antifungal activities of the target compounds were evaluated. The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.
- Xu, Yuan-Yuan,Qian, An-Ran,Cao, Xu-Feng,Ling, Chen-Yu,Cao, Yong-Bing,Wang, Rui-Lian,Li, Yi-Su,Yang, Yu-She
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p. 703 - 706
(2016/05/19)
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- A kind of 3,4-dichloro-thiazole derivatives and process for their preparation and use
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The invention provides 3,4-dichloro isothiazole derivatives, their preparation method and application. The invention relates to a heterocyclic compound containing 3,4-dichloro isothiazol, and the compound is represented by the following chemical structural general formula. The invention discloses the structural general formula of the compound, a synthetic method of the compound and applications of the compound as pesticide, bactericide, anti-plant virus agent, and plant activator, and a technology of mixing the compound with agriculturally acceptable auxiliary agents or synergists for preparing pesticide, bactericide, anti-plant virus agent, and plant activator. The invention further discloses the combined application of the compound and the commercial pesticide, bactericide, anti-plant virus agent, and plant activator in controlling diseases, insect pests, and virus diseases in agriculture, forestry and gardening, and a preparation method of the compound and the commercial pesticide, bactericide, anti-plant virus agent, and plant activator.
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Paragraph 0046-0047; 0095-0096
(2016/10/08)
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- THIAZOLOPYRIMIDINONES AS MODULATORS OF NMDA RECEPTOR ACTIVITY
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The present invention relates to certain thiazolopyrimidinone compounds for use in modulating NMDA receptor activity, pharmaceutical compositions comprising such compounds and methods of treating neurological and psychiatric conditions.
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Paragraph 0335
(2015/04/28)
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- QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
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- HETEROCYCLYL-SUBSTITUTED ANTI-HYPERCHOLESTEROLEMIC COMPOUNDS
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This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts thereof, wherein R12 is a hydroxylated alkyl group and R9 contains a heterocyclic ring. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating atherosclerosis and preventing atherosclerotic disease events.
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Page/Page column 38
(2008/12/05)
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- SYNTHESIS OF TWO NEW THIAZOLE-CONTAINING OLIGOPEPTIDES AS POTENTIAL DNA MINOR GROOVE BINDING ANALOGS OF NETROPSIN
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On the basis of previous studies on synthetic models related to the antibiotic agents Netropsin and Distamycin-A, the design and synthesis of two potential DNA minor groove ligands are described.Methia-Nt and Isothia-Nt were prepared by liquid-phase peptidic synthesis from the key compounds ethyl 2-amino-5-methylthiazole-4-carboxaldehyde (1) and ethyl 2-aminothiazole-5-carboxylate (8) respectively.
- Plouvier, Bertrand,Bailly, Christian,Houssin, Raymond,Henichart, Jean-Pierre
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p. 693 - 701
(2007/10/02)
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- The Preparation of Thiazole-4- and -5-carboxylates, and an Infrared Study of their Rotational Isomers
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Convenient general procedures have been developed for preparing series of thiazole-4- and -5-carboxylates containing alkyl and halogeno substituents.While both series of esters show i.r. carbonyl doublets caused by rotational isomerism, the more intense absorptions of the 4-carboxylates are the lower wavenumber components, whereas those of the 5-carboxylates are the higher wavenumber components.In both series the stronger bands arise from the thermochemically more stable forms; identification of these forms as the carbonyl O,S-syn-s-trans rotamers is more certain with the 4-carboxylates than with the 5-carboxylates.
- Barton, Anne,Breukelman, Stephen P.,Kaye, Perry T.,Meakins, G. Denis,Morgan, David J.
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p. 159 - 164
(2007/10/02)
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