- Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii
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The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3- benzenediamine (18b), which displayed an IC50 value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented.
- Endeshaw, Molla M.,Li, Catherine,Leon, Jessica De,Yao, Ni,Latibeaudiere, Kirk,Premalatha, Kokku,Morrissette, Naomi,Werbovetz, Karl A.
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scheme or table
p. 5179 - 5183
(2010/10/03)
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- Synthesis and Antitubulin Activity of N1- and N 4-Substituted 3,5-Dinitro Sulfanilamides against African Trypanosomes and Leishmania
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Thirty analogues of N1-phenyl-3,5-dinitro-N4,N 4-di-n-propylsulfanilamide (GB-II-5, compound 3), a new antikinetoplastid antimitotic agent, have been synthesized and evaluated. The addition of simple functional groups to the N1 aromatic ring generally decreases antiparasitic and antimitotic potency, but placement of a dibutyl substituent at the N4 nitrogen to give N1-phenyl-3,5-dinitro-N 4,N4-di-n-butylsulfanilamide (compound 35) augments antitrypanosomal and antileishmanial activity. Compound 35 possesses IC 50 values of 0.12 and 2.6 μM against cultured T. brucei and L. donovani amastigote-like forms, surpassing the activity of compound 3 against these parasites by 3.4- and 1.9-fold, respectively. Compound 35 inhibits the assembly of leishmanial tubulin with an IC50 of 6.9 μM and displays antimitotic effects in cultured T. brucei as assessed by flow cytometry, but shows little effect on purified mammalian tubulin, and displays 100-fold selectivity for trypanosomes over two mammalian cell lines. Although 3 and 35 were not effective in initial in vivo antitrypanosomal assays, the in vitro potency and selectivity of these compounds make N 1-aryl-3,5-dinitro-N4,N4-dialkylsulfanilamides a promising new class of antikinetoplastid agents that act on parasite tubulin.
- Bhattacharya, Gautam,Herman, Johnathan,Delfín, Dawn,Salem, Manar M.,Barszcz, Todd,Mollet, Mike,Riccio, Guy,Brun, Reto,Werbovetz, Karl A.
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p. 1823 - 1832
(2007/10/03)
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- Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin.
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Novel dinitroaniline sulfonamides based on the herbicide oryzalin 3 were synthesized and evaluated for activity against the parasitic protozoan Leishmania donovani and against leishmanial tubulin, the putative antiparasitic target of oryzalin. A subset of these compounds possess more activity against both Leishmania and the target protein in vitro. Compound 20 displays improved potency against leishmanial tubulin and is 13.4-fold more active against L. donovani axenic amastigotes than oryzalin.
- Bhattacharya, Gautam,Salem, Manar M,Werbovetz, Karl A
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p. 2395 - 2398
(2007/10/03)
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- Process of improving activity of herbicides and fertilizers using N-(2-hydroxyethyl)-acetamide or -propanamide
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The invention is related to the use of certain water-soluble compounds known as such and having the Formula for the modulation of membrane dependent metabolism processes within living cells, in particular with relation to transport phenomena and cell procedures which are induced or influenced by active agents supplied from outside the cell, products containing these substances for the above described uses and processes using these products.
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- 5,6-Dihydro-1,2,4,6-thiatriazin-5-one-1,1-dioxides
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5,6-Dihydro-1,2,4,6-thiatriazin-5-one-1,1-dioxides of the formula STR1 where R1 is hydrogen, a metal atom or an unsubstituted or substituted ammonium radical, R2 is a saturated or unsaturated straight-chain aliphatic radical of up to 10 carbon atoms, a cycloaliphatic radical or 3 to 7 carbon atoms, a branched saturated or unsaturated aliphatic radical of 3 to 10 carbon atoms, a halogen-, alkoxy- or alkylmercapto-substituted aliphatic radical of 2 to 10 carbon atoms tetrahydrofuryl substituted methyl, a cycloalkoxy-substituted aliphatic radical of 4 to 10 carbon atoms, unsubstituted or halogen-substituted benzyl or phenyl, halophenyl, or alkylphenyl of a total of up to 10 carbon atoms, R3 is hydrogen, a straight-chain aliphatic radical of up to 10 carbon atoms, a cycloaliphatic radical of 3 to 7 carbon atoms, a branched aliphatic radical of 3 to 10 carbon atoms, haloalkyl, or alkoxyalkyl of 2 to 10 carbon atoms and X is oxygen and may also be sulfur if R2 is unsubstituted or halogen-substituted benzyl, processes for their preparation, and herbicides containing the above compounds.
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- Plant-protective and pest-control agent
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A herbicidal composition capable of preventing weed growth of potatoes or soybean plants consists of a triazene or an aromatic nitro compound together with an inorganic salt, especially sodium bisulfate or potassium bisulfate which reduced the quantity of the organic herbicide below that usually required to obtain a corresponding herbicidal effect and hence prevents phytotoxic damage. The composition contains 0.1:1 to 15:1 parts by weight of the inorganic compound to the organic compound and is applied in an amount of 0.1 to 30 kg of the composition per hectare.
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- Certain ethers of certain di and trihalo-1-hydroxy-2-(fluoroalkyl)1H-imidazo(4,5-b)pyridine derivatives
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Ethers of di and trihalo-1-hydroxy-2-(1,1-difluoroalkyl)-1H-imidazo(4,5-b)pyridine compounds, useful as herbicides and rodenticides.
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- Esters of 1-hydroxy-1H-imidazo-(4,5-b)-pyridines as herbicides
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Ethers and esters of 1-hydroxy-2-(1,1-difluoroalkyl)-1H-imidazo(4,5-b)pyridine compounds, useful as herbicides.
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- 1H-imidazo(4,5,-b)-pyridine derivatives
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Ethers and esters of 1-hydroxy-2-(1,1-difluoroalkyl)-1H-imidazo(4,5-b)pyridine compounds, useful as herbicides.
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