527-73-1Relevant articles and documents
Evaluation of (S)- and (R)-misonidazole as GPX inhibitors: Synthesis, characterization including circular dichroism and in vitro testing on bovine GPx-1
Wilde, Felix,Chamseddin, Chamseddin,Lemmerhirt, Heidi,Bednarski, Patrick J.,Jira, Thomas,Link, Andreas
, p. 153 - 160 (2014)
Racemic misonidazole, a radiosensitizer formally used in radiation therapy of cancer and to date still applied, was once reported to exhibit strong inhibitory effects on mouse glutathione peroxidases (GPX). This appeared to qualify misonidazole as a lead structure for the development of novel GPX inhibitors to cause oxidative stress in chemotherapy-resistant tumors. A unique feature of misonidazole as an inhibitor of GPX is the absence of a thiol functionality. Therefore, it was expected to selectively target inhibition devoid of promiscuous interactions with cations and sulfhydryl groups. We synthesized the isomers of misonidazole and analyzed the ability of chiroptical high-performance liquid chromatography (HPLC) to identify the particular enantiomers. Due to the chiral pool synthesis, the assignment of the correct configuration could be verified. Finally, we evaluated both isomers for their inhibitory activities on bovine erythrocyte GPx-1, which is 87% homologous to the human enzyme. Despite the previously reported inhibition of racemic misonidazole on the less homologous mouse GPx-1, we did not find any significant inhibitory activity on the bovine enzyme for either isomer. Though misonidazole appears unlikely to be an inhibitor of human GPx-1 activity, we still spotlight misonidazole as a promising fragment-like lead structure in general. The (S)- and (R)-isomers of misonidazole were synthesized and analyzed for their inhibitory activities on bovine erythrocyte GPx-1, which is 87% homologous to the human enzyme. Although misonidazole was found to be not likely to be an inhibitor of human GPx-1 activity, misonidazole is still spotlighted as a promising fragment-like lead structure in general.
Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study
Assun??o, Elvis L. F.,Carvalho, Diego B.,das Neves, Amarith R.,Kawasoko Shiguemotto, Cristiane Y.,Portapilla, Gisele B.,de Albuquerque, Sergio,Baroni, Adriano C. M.
, p. 2019 - 2028 (2020/09/21)
Chagas disease affects 6–8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50=3.0 μM, SI>65.3), with an IC50=3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3?Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2, 4-CH3?Ph) with IC50=1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.
METHOD FOR MANUFACTURING RADIOACTIVE HALOGEN LABELED COMPOUND
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Paragraph 0039; 0040, (2016/12/22)
PROBLEM TO BE SOLVED: To provide means for efficiently manufacturing a radioactive halogen labeled compound. SOLUTION: There is provided a method for manufacturing a radioactive halogen labeled compound represented by the formula: Sub-X, where Sub represents a substrate and X represents a radioactive halogen atom, and including (1) a process of reacting a high molecular compound containing a substrate and a radioactive halogenated ion under a condition where a phase transfer catalyst exists, (2) a process of binding a byproduct represented by a formula: Sub-OH, where Sub represents a substrate, isolating from the high molecular compound and a compound having an isocyanate group, (3) a process of removing a byproduct bound with the compound having the isocyanate group, and (4) a process of obtaining the radioactive halogen labeled compound from a reaction product of the high molecular compound and the radioactive halogenated ion. COPYRIGHT: (C)2015,JPOandINPIT
