Calcium Phosphate and Bioactive Glasses
Vincenzo Guarino, Marco Antonio Alvarez-Pérez in Current Advances in Oral and Craniofacial Tissue Engineering, 2020
The most commonly used trial to report biocompatibility is the MTT trial. The MTT or Bromide 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazo test is a colorimetric technique that is used to assess cell density (Stockert et al. 2018; Carmichael et al. 1987). This test is based on the fact that a tetrazole salt (yellow color) is reduced to formazan crystals (purple color) in living cells (Mosmann 1983). This reaction occurs because the NAD(P)H-dependent cellular oxidoreductases enzymes can, under defined conditions, reflect the number of viable cells present, by the activity of dehydrogenases (Stockert et al. 2018). After the reduction of MTT, the culture medium is currently removed, the formazan deposits are extracted and the DMSO (Mosmann 1983) is evaluated colorimetrically, usually used for extraction.
Nitroblue Tetrazolium Reduction
Robert A. Greenwald in CRC Handbook of Methods for Oxygen Radical Research, 2018
In the oxidized form, NBT chloride is a yellow compound soluble in aqueous mixtures. Its reduction to formazan is accompanied by disappearance of the positive charges, resulting in a substantial decrease in solubility, as well as disruption of the tetrazole rings with a marked modification of the absorption spectrum in the visible region (Figure 2) and the appearance of intense blue color. In buffered aqueous solutions at near-neutral pH, the molar extinction coefficient in the 550-nm range is about 15,000 M−1 cm−1 for the monoformazan (NBT+, Cl−) and 30,000 M−1 cm−1 for the diformazan. The extent of NBT reduction can be measured by spectrophotometry, although such assays are limited by the relative insolubility of formazan in aqueous solutions.
Tedizolid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Structural activity relationships exist for oxazolidinones. Although all oxazolidinones possess A, B, and C rings, the A-ring C5 substituent, optimized C rings, and added D rings appear to be most associated with improved antibacterial activity (Michalska et al., 2013). Tedizolid possesses a hydro- xymethyl group at the A-ring C5 position, in contrast to the acetamide substituent of linezolid (Michalska et al., 2013). As mentioned previously, this substitution is believed to preserve tedizolid activity against cfr-mediated linezolid-resistant bacteria. In addition, tedizolid possesses a pyridine C ring, as well as a tetrazole D ring that is absent in linezolid (Locke et al., 2010; Michalska et al., 2013). The C and D rings of tedizolid are believed to confer increased potency by creating two additional hydrogen bonds to 23S rRNA residues A2451 and U2584, which may stabilize the drug–PTC interaction (Shaw et al., 2008). In contrast, hydrophobic interactions between these residues and the oxazolidinone B ring may occur with linezolid. Owing to additional contact with the PTC, tedizolid binding appears less reliant on the residues involved in linezolid binding (Shaw et al., 2008).
An overview of current and emerging antifungal pharmacotherapy for invasive fungal infections
Published in Expert Opinion on Pharmacotherapy, 2021
Scott W. Mueller, Sonya K. Kedzior, Matthew A. Miller, Paul M. Reynolds, Tyree H. Kiser, Martin Krsak, Kyle C. Molina
Tetrazoles offer many potential advantages over triazoles, namely safety, tolerability, spectrum, potency and fewer DDIs. VT-1598 offers a wider range of activity compared to oteseconazole and VT-1129. This agent has superior in vitro activity against resistant strains, such as C. auris, potentially broadening its use as a first-line therapy for resistant yeast and mold infections pending clinical efficacy and safety data. VT-1129 is an exciting future option for cryptococcal meningitis, especially for fluconazole-resistant isolates. Tetrazoles will also be an attractive prophylaxis option where triazoles would otherwise be indicated. Future superiority or non-inferiority trials and registries comparing tetrazole efficacy and cost-effectiveness to triazoles are needed to define their role in therapy. Tetrazoles may eventually replace triazoles in many indications.
Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Chao Wang, Yuelin Li, Zi Liu, Zeyu Wang, Zihan Liu, Shuai Man, Yujing Zhang, Kai Bao, Yingliang Wu, Qi Guan, Daiying Zuo, Weige Zhang
To further understand the binding interactions, molecular docking of the most active compound 6–31 was carried out with tubulin crystal structure (PDB code: 3HKC) using the CDOCKER programme of Discovery Studio 3.0 software. As shown in Figure 6, XRP44X and compound 6–31 are located at the same position with a similar conformation in the binding pocket. Meanwhile, the hydrogen bond exists between the carbonyl group of XRP44X or compound 6–31 with amino acid residue Alaβ317. Moreover, it is worth noting that the residue of Asnβ258 forms a hydrogen bond with the 2 N of 1H-tetrazole of compound 6–31 and the residue of Lysβ352 forms a hydrogen bond with the 4 N of 1H-tetrazole of compound 6–31. It suggests that the 1H-tetrazole derivatives can not only maintain the right conformation, but also nicely nestle in the active site. The 1H-tetrazole moiety and unique active site interactions set the stage for structure-based design of more potent derivatives.
Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Mikhail Krasavin, Raivis Žalubovskis, Aiga Grandāne, Ilona Domračeva, Petr Zhmurov, Claudiu T. Supuran
Reagents and starting materials were obtained from commercial sources (Sigma-Aldrich, St. Louis, MO) and used as received. The solvents were purified and dried by standard procedures prior to use; petroleum ether of boiling range 40–60° C was used. Flash chromatography was carried out using Merck silica gel (230–400 mesh). Thin-layer chromatography was performed on silica gel, spots were visualised with UV light (254 and 365 nM). Melting points were determined on an OptiMelt automated melting point system. IR spectra were measured on a Shimadzu FTIR IR Prestige-21 spectrometer. NMR spectra were recorded on Varian Mercury (400 MHz) spectrometer with chemical shifts values (d) in ppm relative to TMS using the residual DMSO-d6 signal as an internal standard. Elemental analyses were performed on a Carlo Erba CHNSeO EA-1108 apparatus. Starting material sulfocoumarins (418 and 519) were prepared as described previously. Alkynes employed in the synthesis of 1a–b are commercially available. Tetrazoles employed in the synthesis of 1c–d were prepared according to the literature protocols20,21. All reagents for biological assays were purchased from Sigma (St. Louis, MO).
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