Disease relevance of thiazole

• The 1.87 A-resolution structure of the radical form of PFOR from Desulfovibrio africanus shows that, despite currently accepted ideas, the thiazole ring of the ThDP cofactor is markedly bent, indicating a drastic reduction of its aromaticity [1].
• Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: identification of an acyldisulfide-linked protein--protein conjugate that is functionally analogous to the ubiquitin/E1 complex [2].
• Thiamin biosynthesis in Escherichia coli and Bacillus subtilis show some similarities, but diverge at key steps of thiazole formation [3].
• Inhibition of herpes simplex virus replication by a 2-amino thiazole via interactions with the helicase component of the UL5-UL8-UL52 complex [4].
• The compound with the best activity/toxicity ratio contains an alkyl sulfonyl substituent on the thiazole ring [5].

High impact information on thiazole

• BACKGROUND & AIMS: Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release [6].
• This suggests that thiazole rings are part of the MccB17 structure recognized by SbmA [7].
• A novel isothiazole, CP-547,632, was identified as a potent inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases (IC(50) = 11 and 9 nM, respectively) [8].
• Structure of the Thiazole Biosynthetic Enzyme THI1 from Arabidopsis thaliana [9].
• Meanwhile, in vitro studies with microcin B17 have helped to uncover the molecular mechanisms by which post-translational modification results in the formation of heterocyclic oxazole and thiazole rings [10].

Chemical compound and disease context of thiazole

• BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains four oxazole and four thiazole rings, and inhibits DNA gyrase [11].
• Also, compared to flurbiprofen, the thiazole had less anti-inflammatory activity in the hind-paw edema test [12].
• Cytotoxic activity measurements for cis,cis,trans-[Ru(PPh(3))(N-THZ)(N(7),S -H(2)TP)(2)]Cl(2) (4) (THZ = thiazole, H(2)TP = 6-thiopurine) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-HTPR)2]Cl(2) (5) (HTPR = 6-thiopurine riboside) against ovarian cancer cells A2780/S gave IC(50) values of 17 +/- 1 and 29 +/- 9 microM, respectively [13].
• The origin of the carbon chain in the thiazole moiety of thiamine in Escherichia coli: incorporation of deuterated 1-deoxy-D-threo-2-pentulose [14].
• Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC(90)=0.06 microg/mL) and vancomycin resistant Enterococcus spp [15].

Biological context of thiazole

• The latter conclusion is based on an analysis of the mobilities of the multiple HSFDT-DNA complexes and on a two-color mobility-shift fluorescence assay that uses a mutant of HSFDT engineered for site-specific labeling with fluorescein and target DNA labeled with an "energy transfer" dye, thiazole orange-thiazole blue heterodimer [16].
• Asymmetric hydrogenation of trisubstituted olefins with iridium-phosphine thiazole complexes: a further investigation of the ligand structure [17].
• BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains thiazole and oxazole heterocycles derived from a distributive yet directional cyclization of cysteines and serines in the McbA precursor catalyzed by MccB17 synthetase [18].
• With the use of a high-throughput biochemical DNA helicase assay as a screen, T157602, a 2-amino thiazole compound, was identified as a specific inhibitor of herpes simplex virus (HSV) DNA replication [4].
• Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: synthesis and structure-activity relationships [19].

Anatomical context of thiazole

• Structural basis for contrasting activities of ribosome binding thiazole antibiotics [20].
• The Vmax for the hydrolysis of CEO by hepatic microsomes from thiazole-treated rats (13.4 nmol/min/mg protein) was 1.5-fold greater than that with microsomes from pyrazine-treated rats, whereas similar Km values (approximately 1 mM) were observed for both microsomal preparations [21].
• Medial smooth muscle cell proliferation in the balloon injured rabbit aorta: effect of a thiazole compound with platelet inhibitory activity [22].
• The biological activity of each enantiomer was evaluated in intact mouse macrophages and in human whole blood and showed that, of these three series, only the thiazole is enantioselective and that the active configuration is (S) (being between 2 and 3 orders of magnitude more potent than the (R) isomer in mouse macrophages) [23].
• Analogues with higher cytotoxicity such as 2 which retain the thiazole ring of the natural product proved effective in completely inhibiting the cell proliferation of breast, colon, and lung tumor cell lines at 1.5 microM concentration compared to a 70 microM dose level of 5-fluorouracil [24].

Associations of thiazole with other chemical compounds

• Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis [25].
• In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models [26].
• An analogue program designed to reduce photosensitivity from that compound eventually led to the discovery that the indole ring could be replaced by a simple thiazole, This resulted in the experimental cyclooxygenase inhibitor itazagrel [27].
• The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues [28].
• These histamine-induced effects were mimicked by the histamine H1 receptor agonist 2-(2-aminoethyl) thiazole dihydrochloride (10 microM) and blocked by the H1 antagonists pyrilamine (100 nM) or diphenhydramine (100 nM) [29].

Gene context of thiazole

• N.crassa CyPBP37 is able to functionally replace Thi4p in yeast thiazole synthesis [30].
• A cDNA clone, pAgthi1, encoding a homologue of yeast Thi4, which is involved in thiazole biosynthesis, was isolated from a library made from poly(A) RNA from actinorhizal nodules of Alnus glutinosa by differential screening with nodule and root cDNA, respectively [31].
• Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole [32].
• Novel thiazole based heterocycles as inhibitors of LFA-1/ICAM-1 mediated cell adhesion [33].
• SK&F 86002 [5-(4-pyridyl)-6(4-fluorophenyl)-2,3-dihydroimidazo(2,1-b) thiazole], a potent cytokine-suppressive anti-inflammatory agent, has been shown to inhibit cyclooxygenase (CO) and 5-lipoxygenase (LO) activity and to inhibit the production of cytokines both in vitro and in vivo [34].

Analytical, diagnostic and therapeutic context of thiazole

• The molecular structure of PatJ(1), determined by X-ray crystallography, has a saddle conformation with two close-to-coparallel thiazole rings, very similar to the geometry of patellamide D [35].
• The thiazole derivative inhibited platelet aggregation following oral administrative inhibited platelet aggregation following oral administration in five laboratory species [12].
• Using a PCR approach to clone a thiazole-forming nonribosomal peptide synthetase (NRPS) as a probe, we localized a 172-kb DNA region from S. atroolivaceus S-140 that harbors the lnm biosynthetic gene cluster [36].
• Separate condensation of other chiral (8 and 13) and racemic (18) amino thiols as auxiliary with rac-4, (4S)-4, or (4R)-4 is accompanied by an in situ crystallization-induced dynamic resolution, whereby one distereomer of thiazole template selectively precipitates and can be isolated by simple filtration in 76-82% yield with dr > 99 [37].
• Pairing LDS-751, thiazole blue, or TO-PRO-3 with propidium iodide (PI) for flow cytometry allowed the differentiation of cells containing BrdUrd from BrdUrd unlabeled cells [38].

References