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Nitroimidazoles

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https://www.readbyqxmd.com/read/29746214/a-two-component-assay-for-hypoxia-incorporating-long-term-nitroreduction-and-short-term-dna-damage-allows-differentiation-of-the-three-hypoxia-sub-types
#1
Cameron J Koch
Hypoxia in tumors has many well-characterized effects that are known to prevent optimal cancer treatment. Despite the existence of a large number of assays that have supported hypoxia as an important diagnostic, there is no routine clinical assay in use, and anti-hypoxia therapies have often not included parallel hypoxia measurements. Even with a functioning hypoxia assay, it is difficult to match the oxygen dependence of treatment resistance to that of the assay, and this mismatch can vary substantially from assay to assay and even from tumor to tumor [e...
May 10, 2018: Radiation Research
https://www.readbyqxmd.com/read/29736775/5-nitroimidazole-derived-schiff-bases-and-their-copper-ii-complexes-exhibit-potent-antimicrobial-activity-against-pathogenic-anaerobic-bacteria
#2
Alexandre A Oliveira, Ana P A Oliveira, Lucas L Franco, Micael O Ferencs, João F G Ferreira, Sofia M P S Bachi, Nivaldo L Speziali, Luiz M Farias, Paula P Magalhães, Heloisa Beraldo
In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Parabacteroides distasonis and Fusubacterium nucleatum pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases...
May 7, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29730454/phase-solubility-studies-and-anti-trichomonas-vaginalis-activity-evaluations-of-metronidazole-and-methylated-%C3%AE-cyclodextrin-complexes-comparison-of-crysmeb-and-rameb
#3
Sophia Malli, Christian Bories, Gilles Ponchel, Philippe M Loiseau, Kawthar Bouchemal
Metronidazole (MTZ) is a 5-nitroimidazole drug used for the treatment of Trichomonas vaginalis parasitic infection. Aqueous formulations containing MTZ are restricted because apparent solubility in water of this drug is low. In this context, two methylated-β-cyclodextrins (CRYSMEB and RAMEB) were used as a tool to increase apparent solubility of MTZ in water. CRYSMEB was limited by its own solubility in water (15% w/w, 12.59 mM), while RAMEB at a concentration of 40% w/w (300.44 mM) allowed a maximal increase of apparent solubility of MTZ (3...
April 27, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29715780/femtosecond-laser-induced-breakdown-spectroscopy-based-standoff-detection-of-explosives-and-discrimination-using-principal-component-analysis
#4
Abdul Kalam Shaik, Nageswara Rao Epuru, Hamad Syed, Chandu Byram, Venugopal Rao Soma
We report the standoff (up to ~2 m) and remote (~8.5 m) detection of novel high energy materials/explosive molecules (Nitroimidazoles and Nitropyrazoles) using the technique of femtosecond laser induced breakdown spectroscopy (LIBS). We utilized two different collection systems (a) ME-OCT-0007 (commercially available) and (b) Schmidt-Cassegrain telescope for these experiments. In conjunction with LIBS data, principal component analysis was employed to discriminate/classify the explosives and the obtained results in both configurations are compared...
April 2, 2018: Optics Express
https://www.readbyqxmd.com/read/29671618/novel-naphthalimide-nitroimidazoles-as-multitargeting-antibacterial-agents-against-resistant-acinetobacter-baumannii
#5
Jie Kang, Lavanya Gopala, Vijai Kumar Reddy Tangadanchu, Wei-Wei Gao, Cheng-He Zhou
AIM: The increasing emergence of resistant bacteria imposed an urgent request to discover novel antibacterial agents. This work was to develop naphthalimide nitroimidazoles as potentially antibacterial agents. Results/methodology: Compound 9e showed the strong antibacterial activity (minimal inhibitory concentration = 0.013 μmol/ml) against resistant Acinetobacter baumannii (A. baumannii) with rapid killing effect and no obvious triggering of the development of resistance. Its combination use with chloromycin, norfloxacin or clinafloxacin improved the antibacterial potency...
April 19, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29661865/modeling-and-simulation-of-pretomanid-pharmacokinetics-in-pulmonary-tuberculosis-patients
#6
Michael A Lyons
Pretomanid is a nitroimidazole antibiotic in late phase clinical testing as a component of several novel antituberculosis (anti-TB) regimens. A population pharmacokinetic model for pretomanid was constructed using a Bayesian analysis of data from two phase 2 studies, PA-824-CL-007 and PA-824-CL-010, conducted with newly diagnosed adult (median age 27 years) pulmonary TB patients in Cape Town, South Africa. Combined, these studies included 63 males and 59 females administered once daily oral pretomanid doses of 50, 100, 150, 200, 600, 1000, or 1200 mg for 14 days...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29652141/insights-into-2-and-4-5-nitroimidazole-decomposition-into-relevant-ions-and-molecules-induced-by-vuv-ionization
#7
A Cartoni, A R Casavola, P Bolognesi, M C Castrovilli, D Catone, J Chiarinelli, R Richter, L Avaldi
Nitromidazoles are relevant compounds of multidisciplinary interest, and knowledge of their physical-chemical parameters as well as their decomposition under photon irradiation is needed. Here we report an experimental and theoretical study of the mechanisms of VUV photofragmentation of 2- and 4(5)-nitromidazoles, compounds used as radiosensitizers in conjunction with radiotherapy as well as high-energy density materials. Photoelectron-photoion coincidence experiments, measurements of the appearance energies of the most important ionic fragments, density functional theory, and single-point coupled cluster calculations have been used to provide an overall insight into the energetics and structure of the different ionic/neutral products of the fragmentation processes...
April 13, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29595104/association-of-metronidazole-with-cancer-a-potential-risk-factor-or-inconsistent-deductions
#8
Muhammad Adil, Waheed Iqbal, Fazal Adnan, Shabnam Wazir, Imran Khan, Mohammad Umar Khayam, Mohammad Amjad Kamal, Shafiq Ahmad, Jawad Ahmad, Ishaq N Khan
Metronidazole is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and protozoal parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, acute ulcerative gingivitis, syphilis and tropical phagedena. In addition to its toxicity in the gastrointestinal tract and central/peripheral nervous system, metronidazole has been reported to cause mucosal imbalance by affecting the expression of mucin (Muc2 gene), which is responsible to form an insoluble mucous barrier that protects the gut lumen from microbial colonization...
March 29, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29572567/anti-trichomonas-vaginalis-activity-of-ursolic-acid-derivative-a-promising-alternative
#9
Fernanda Gobbi Bitencourt, Patrícia de Brum Vieira, Lucia Collares Meirelles, Graziela Vargas Rigo, Elenilson Figueiredo da Silva, Simone Cristina Baggio Gnoatto, Tiana Tasca
Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T...
March 23, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29551480/alkylated-aminated-nitroimidazoles-and-nitroimidazole-7-chloroquinoline-conjugates-synthesis-and-anti-mycobacterial-evaluation
#10
Shalini, Albertus Viljoen, Laurent Kremer, Vipan Kumar
The success in exploring anti-tubercular potency of nitroimidazole and quinoline, the core moieties of recently approved anti-tubercular drugs instigated us to synthesize a series of alkylated/aminated 2-methyl-5-nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates and to evaluate them for their activities against Mycobacterium tuberculosis as well as for their cytotoxicity towards the J774 murine macrophage cell line. Although the synthesized compounds did not surpass the activity of the standard drug Isoniazid, they have appreciable activities with minimal cytotoxicity...
March 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29544148/recent-advances-of-imidazole-containing-derivatives-as-anti-tubercular-agents
#11
REVIEW
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29518721/determination-of-the-sulfate-and-glucuronide-conjugates-of-levornidazole-in-human-plasma-and-urine-and-levornidazole-and-its-five-metabolites-in-human-feces-by-high-performance-liquid-chromatography-tandem-mass-spectrometry
#12
Gaoli He, Beining Guo, Jing Zhang, Yi Li, Xiaojie Wu, Yaxin Fan, Yuancheng Chen, Guoying Cao, Jicheng Yu
Levornidazole is a novel third-generation nitroimidazoles antibiotic which metabolism and disposition in human are not well known. We have previously developed two methods to quantify levornidazole and its phase I metabolites, Ml (Hydroxylation metabolite), M2 (N-dealkylation metabolite) and M4 (Oxidative dechlorination metabolite), in human plasma and urine. In this study, we developed three novel liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods and analyzed its phase II metabolites, sulfate conjugate (M6) and glucuronide conjugate (M16), in human plasma and urine, and the parent drug and above-mentioned five metabolites in human feces samples...
April 1, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29511378/simultaneous-determination-of-nitroimidazoles-and-quinolones-in-honey-by-modified-quechers-and-lc-ms-ms-analysis
#13
Haiyan Lei, Jianbo Guo, Zhuo Lv, Xiaohong Zhu, Xiaofeng Xue, Liming Wu, Wei Cao
This study reports an analytical method for the determination of nitroimidazole and quinolones in honey using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A modified QuEChERS methodology was used to extract the analytes and determine veterinary drugs in honey by LC-MS/MS. The linear regression was excellent at the concentration levels of 1-100 ng/mL in the solution standard curve and the matrix standard curve. The recovery rates of nitroimidazole and quinolones were 4.4% to 59.1% and 9.8% to 46...
2018: International Journal of Analytical Chemistry
https://www.readbyqxmd.com/read/29485279/development-and-validation-of-a-hybrid-screening-and-quantitative-method-for-the-analysis-of-eight-classes-of-therapeutants-in-aquaculture-products-by-liquid-chromatography-tandem-mass-spectrometry
#14
Ryan S Gibbs, Shauna L Murray, Lynn V Watson, Brandy P Nielsen, Ross A Potter, Cory J Murphy
A method using reverse-phase ultra-high-performance liquid chromatography coupled with tandem mass spectrometry is described for eight classes of therapeutants that are used in marine aquaculture products. Validation studies to evaluate recovery, precision, method detection limits, and measurement uncertainty were performed at three levels, using three representative matrices [salmon (fatty fish), tilapia (lean fish), and shrimp (crustaceans)] to assess the method performance for use as a screening or determinative (quantitative and confirmatory) method...
February 27, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29478545/simple-and-rapid-determination-of-5-nitroimidazoles-and-metabolites-in-fish-roe-samples-by-salting-out-assisted-liquid-liquid-extraction-and-uhplc-ms-ms
#15
Maykel Hernández-Mesa, Carmen Cruces-Blanco, Ana M García-Campaña
A novel multiresidue method is proposed for the determination of 12 5-nitroimidazoles and their metabolites in fish roe samples using UHPLC-MS/MS. A salting-out assisted liquid-liquid extraction procedure was performed prior to sample analysis. The separation of compounds was accomplished using a C18 Zorbax Eclipse Plus column (50 mm × 2.1 mm, 1.8 µm) at 25 °C and a mobile phase consisting of 0.025% (v/v) aqueous formic acid and pure MeOH at a flow rate of 0.5 mL/min. Parameters involved in ionization and fragmentation were also optimized...
June 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29444462/photodynamic-therapy-as-a-new-approach-to-trichomonas-vaginalis-inactivation
#16
Thaisa Helena Silva Fonseca, Marina Alacoque, Fabrício Marcus Silva Oliveira, Betânia Maria Soares, Henrique Vitor Leite, Marcelo Vidigal Caliari, Maria Aparecida Gomes, Haendel Busatti
The emergence of nitroimidazole resistant isolates has been an aggravating factor in the treatment of trichomoniasis, the most common non-viral sexually transmitted disease in the world. This particularity highlights the importance of new technologies that are safe, effective, and have minor side effects or resistance. Hence, we evaluated the effectiveness of photodynamic therapy on the inactivation of Trichomonas vaginalis in vitro. We used methylene blue as a photosensitizing substance, and a light-emitting diode (LED) for irradiation of metronidazole sensitive and resistant strains...
February 11, 2018: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29425734/in-vitro-and-in-vivo-pharmacodynamics-of-three-novel-antileishmanial-lead-series
#17
M Van den Kerkhof, D Mabille, E Chatelain, C E Mowbray, S Braillard, S Hendrickx, L Maes, G Caljon
OBJECTIVES: Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential new drug leads for leishmaniasis. Pharmacodynamics studies included both in vitro and in vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs and evaluation of their cidal activity potential. METHODS: Efficacy against the reference laboratory strains of Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) and L...
April 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29412643/the-expanding-diversity-of-mycobacterium-tuberculosis-drug-targets
#18
Samantha Wellington, Deborah T Hung
After decades of relative inactivity, a large increase in efforts to discover antitubercular therapeutics has brought insights into the biology of Mycobacterium tuberculosis (Mtb) and promising new drugs such as bedaquiline, which inhibits ATP synthase, and the nitroimidazoles delamanid and pretomanid, which inhibit both mycolic acid synthesis and energy production. Despite these advances, the drug discovery pipeline remains underpopulated. The field desperately needs compounds with novel mechanisms of action capable of inhibiting multi- and extensively drug -resistant Mtb (M/XDR-TB) and, potentially, nonreplicating Mtb with the hope of shortening the duration of required therapy...
February 15, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29404665/target-screening-of-105-veterinary-drug-residues-in-milk-using-uhplc-esi-q-orbitrap-multiplexing-data-independent-acquisition
#19
Jian Wang, Daniel Leung, Willis Chow, James Chang, Jon W Wong
This paper presents a multi-class target screening method for the detection of 105 veterinary drug residues from 11 classes in milk using ultra-high performance liquid chromatography electrospray ionization quadrupole Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap). The method is based on a non-target approach of full mass scan and multiplexing data-independent acquisition (Full MS/mDIA). The veterinary drugs include endectocides, fluoroquinolones, ionophores, macrolides, nitroimidazole, NSAIDs, β-lactams, penicillins, phenicols, sulfonamides, and tetracyclines...
February 5, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29391293/a-case-of-non-treated-trichomonas-vaginalis-infection-and-severe-preterm-labor-with-positive-obstetrical-outcome
#20
E Salakos, D Korb, C Morin, O Sibony
Trichomonas vaginalis is a very common, sexually transmitted, infection that may sometimes be asymptomatic or cause vaginitis and urethritis. Recently, it has been associated with adverse obstetric outcomes such as preterm delivery, low birth weight and premature rupture of membranes. Trichomonas vaginalis can be vertically transmitted at birth. It has been found in pharynx and low respiratory tract of neonates with respiratory disease. It has also been involved in some cases of intellectual disability. The recommended treatment is a 2g metronidazole oral single dose, even for asymptomatic patients...
April 2018: Journal of Gynecology Obstetrics and Human Reproduction
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