19622-55-0Relevant articles and documents
Trypanosoma cruzi: Effect and mode of action of nitroimidazole and nitrofuran derivatives
Maya, Juan Diego,Bollo, Soledad,Nunez-Vergara, Luis J.,Squella, Juan A.,Repetto, Yolanda,Morello, Antonio,Perie, Jacques,Chauviere, Gerard
, p. 999 - 1006 (2003)
With the aim of determining the actual target(s) of nitro-group bearing compounds considered as possible leads for the development of drugs against Chagas' disease, we studied in parallel nitrofurans and nitroimidazoles. We investigated nine representative compounds for the following properties: efficacy on different Trypanosoma cruzi strains, redox cyclers, inhibition of respiration, production of corresponding nitroso derivatives and intracellular thiol scavengers. Our results indicate that nifurtimox and related compounds act as redox cyclers, whereas the most active in the series, the 5-nitroimidazole megazol essentially acts as thiol scavenger particularly for trypanothione, the cofactor for trypanothione reductase, an essential enzyme in the detoxification process.
Synthesis of 2-amino-5-(1-methyl-5-nitro-[4-3H]-2-imidazolyl)-1,3,4- thiadiazole
Chauviere,Rousseau,Pillon,Perie
, p. 47 - 51 (1998)
2-Amino-5-(1-methyl-5-nitro-4-iodo-2-imidazoyl)-1,3,4-thiadiazole (5) was prepared from imidazole via a 4-steps sequence. Reductive desiodination of 5 using a tetrahydrofuran solution of NaBH4 in the presence of tritiated water provided the title compound (specific radioactivity 12.6 Ci/mmol) in one step.
5-Nitroimidazole-based 1,3,4-Thiadiazoles: Heterocyclic analogs of metronidazole as anti-helicobacter pylori agents
Moshafi, Mohammad Hassan,Sorkhi, Maedeh,Emami, Saeed,Nakhjiri, Maryam,Yahya-Meymandi, Azadeh,Negahbani, Amir Soheil,Siavoshi, Farideh,Omrani, Maryam,Alipour, Eskandar,Vosooghi, Mohsen,Shafiee, Abbas,Foroumadi, Alireza
, p. 178 - 183 (2011/10/08)
A series of 5-nitroimidazole-based 1,3,4-thiadiazoles were prepared and tested for antibacterial activity against Helicobacter pylori. The anti-H. pylori activity of target compounds along with the commercially available antimicrobial metronidazole was evaluated by comparing the inhibition-zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates it is evident that piperazinyl, 4-methylpiperazinyl, 3-methylpiperazinyl, and 3,5-dimethylpiperazinyl analogs (6a, 6b, 6e, and 6f, respectively) and pyrrolidine derivative 7 had strong activity at 0.5 μg/disc (average of inhibition zone >20 mm) while metronidazole had no activity at this dose. Compound 6f containing the 3,5-dimethylpiperazinyl moiety at the 2-position of the 5-(1-methyl-5-nitro-1H- imidazol-2-yl)-1,3,4-thiadiazole skeleton was the most potent compound tested at low concentrations.
Discovery of a novel nitroimidazolyl-oxazolidinone hybrid with potent anti Gram-positive activity: Synthesis and antibacterial evaluation
Khalaj, Ali,Nakhjiri, Maryam,Negahbani, Amir Soheil,Samadizadeh, Marjaneh,Firoozpour, Loghman,Rajabalian, Saeed,Samadi, Nasrin,Faramarzi, Mohammad Ali,Adibpour, Neda,Shafiee, Abbas,Foroumadi, Alireza
scheme or table, p. 65 - 70 (2011/02/25)
A number of linezolid analogues containing a nitroaryl-1,3,4-thiadiazole moiety, were prepared and evaluated as antibacterial agents against a panel of Gram-positive and Gram-negative bacteria. Among synthesized compounds, nitrofuran analogue 1b exhibited more potent inhibitory activity, with respect to other synthesized compounds and reference drug linezolid. The target compounds were also assessed for their cytotoxic activity against normal mouse fibroblast (NIH/3T3) cells using MTT assay. The results indicated that compound 1c exhibit potent antibacterial activity against Gram-positive bacteria at non-cytotoxic concentrations.
Nitroimidazolyl-1,3,4-thiadiazole-based anti-leishmanial agents: Synthesis and in vitro biological evaluation
Poorrajab, Fatemeh,Ardestani, Sussan Kabudanian,Emami, Saeed,Behrouzi-Fardmoghadam, Mina,Shafiee, Abbas,Foroumadi, Alireza
body text, p. 1758 - 1762 (2009/05/27)
A series of 1-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines were synthesized and evaluated in vitro against Leishmania major. Most of the target compounds exhibited good anti-leishmanial activity against the promastigote form of L. major at non-cytotoxic concentrations. The most active compound was 1-[(5-chloro-2-thienyl)carbonyl]-4-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazol-2-yl]piperazine (5f) with an IC50 value of 9.35 ± 0.67 μM against L. major promastigotes. In addition, this compound was effective against intracellular L. major and significantly decreased the infectivity index.
Synthesis and anti-Helicobacter pylori activity of 5-(nitroaryl)-1,3,4-thiadiazoles with certain sulfur containing alkyl side chain
Foroumadi, Alireza,Rineh, Ardeshir,Emami, Saeed,Siavoshi, Farideh,Massarrat, Sadegh,Safari, Fatemeh,Rajabalian, Saeed,Falahati, Mehraban,Lotfali, Ensieh,Shafiee, Abbas
scheme or table, p. 3315 - 3320 (2009/04/11)
A series of 5-(nitroaryl)-1,3,4-thiadiazoles bearing certain sulfur containing alkyl side chain similar to pendent residue in tinidazole molecule were synthesized and evaluated against Helicobacter pylori using disk diffusion method. The synthesized compounds were also evaluated for their antibacterial, antifungal and cytotoxic effects. Study of the structure-activity relationships of this series of compounds indicated that both the structure of the nitroaryl unit and the pendent group on 2-position of 1,3,4-thiadiazole ring dramatically impact the anti-H. pylori activity. While compound 7a containing 2-[2-(ethylsulfonyl)ethylthio]-side chain from nitrothiophene series was the most potent compound tested against clinical isolates of H. pylori, however, nitroimidazoles 6c and 7c were found to be more promising compounds because of their respectable anti-H. pylori activity besides less cytotoxic effects.
Synthesis and antimycobacterial activity of some alkyl [5-(nitroaryl)-1,3, 4-thiadiazol-2-ylthio]propionates
Foroumadi, Alireza,Kargar, Zahra,Sakhteman, Amirhossein,Sharifzadeh, Zahra,Feyzmohammadi, Robabeh,Kazemi, Mahnoush,Shafiee, Abbas
, p. 1164 - 1167 (2007/10/03)
Two series of 2- and 3-[5-(nitroaryl)-1,3,4-thiadiazol-2-ylthio, sulfinyl and sulfonyl] propionic acid alkyl esters were synthesized and screened for antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. The MIC values for the compounds showing more than 90% inhibition were determined. The result of comparison between two groups of data exhibited that among the synthesized derivatives, the compound propyl 3-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-ylthio]propionate was the most active one (MIC = 1.56 μg ml-1).
Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead
Chauvière, Gérard,Bouteille, Bernard,Enanga, Bertin,De Albuquerque, Cristina,Croft, Simon L.,Dumas, Michel,Périé, Jacques
, p. 427 - 440 (2007/10/03)
As part of our efforts to develop new compounds aimed at the therapy of parasitic infections, we synthesized and assayed analogues of a lead compound megazol, 5-(1-methyl-5-nitro-1H-2-imidazolyl)-1,3,4-thiadiazol-2-amine, CAS no. 19622-55-0), in vitro. We first developed a new route for the synthesis of megazol. Subsequently several structural changes were introduced, including substitutions on the two rings of the basic nucleus, replacement of the thiadiazole by an oxadiazole, replacement of the nitroimidazole part by a nitrofurane or a nitrothiophene, and substitutions on the exocyclic nitrogen atom for evaluation of an improved import by the glucose or the purine transporters. Assays of the series of compounds on the protozoan parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani, as either extracellular cells or infected macrophages, indicated that megazol was more active than the derivatives. Megazol was then evaluated on primates infected with Trypanosoma brucei gambiense, including late-stage central nervous system infections in combination with suramin. Full recovery was observed in five monkeys in the study with no relapse of parasitemia within a 2 year follow-up. Because there is a lack of efficacious treatments for sleeping sickness in Africa and Chagas disease in South America, megazol is proposed as a potential alternative. The mutagenicity of this compound is at present being reevaluated, and metabolism is also under investigation prior to possible further developments.
Synthesis and in vitro antibacterial activity of some N-(5-aryl-1,3,4-thiadiazole-2-yl)piperazinyl quinolone derivatives
Foroumadi, Alireza,Soltani, Fatemeh,Moshafi, Mohammad Hasan,Ashraf-Askari, Rogheeyeh
, p. 1023 - 1028 (2007/10/03)
A series of N-[5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole-2-yl] and N-[5-(nitrophenyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolone derivatives (5a-c and 5d-l) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria. The antibacterial data revealed that all nitroimidazole derivatives (5a-c) showed interesting activity against tested Gram-positive bacteria (minimum inhibitory concentration, MIC=0.008-0.03 μg/ml) while they did not show good activity against Gram-negative organisms. Despite the significant activity of nitroimidazole series, all nitrophenyl analogues (5d-l) were inactive against both Gram-positive and Gram-negative bacteria. Among all of the tested compounds, 5a (ciprofloxacin derivative in nitroimidazole series) exhibited excellent activity against Staphylococcus aureus and Staphylococcus epidermidis (MIC=0.008 μg/ml).
Synthesis and in vitro antifungal activity of 2-aryl-5-phenylsulfonyl- 1,3,4-thiadiazole derivatives
Foroumadi, Alireza,Daneshtalab, Mohsen,Shafiee, Abbas
, p. 1035 - 1038 (2007/10/03)
The synthesis and antifungal activity of a series of 2-nitroaryl-5- phenylsulfonyl-1,3,4-thiadiazoles (5a-e) are described. The in vitro antifungal activity of the compounds was determined against a variety of fungal strains in comparison to miconazole (CAS 22916-47-8) and fluconazole (CAS 86386-73-4). Two derivatives (5d, 5e) showed high activity against Candida albicans and Candida spp. having MIC values ranging from 0.048-3.12 μg/ml, providing higher potencies than the reference drug fluconazole. Compound 5a also showed high activity against Cryptococcus neoformans (MIC 0.048 μg/ml). The activity of this compound against Aspergillus niger and Aspergillus fumigatus was moderate (MIC = 1.56-6.25 μg/ml), while fluconazole was inactive. Moreover, the nitroimidazole derivative 5d possessed good activity against most fungal strains in comparison to fluconazole.
