- Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?
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The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 μM and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 μM). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 ± 0.37 μM). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.
- Terzi?, Natasa,Konstantinovi?, Jelena,Tot, Miklo?,Burojevi?, Jovana,Djurkovi?-Djakovi?, Olgica,Srbljanovi?, Jelena,?tajner, Tijana,Verbi?, Tatjana,Zlatovi?, Mario,Machado, Marta,Albuquerque, Inês S.,Prudêncio, Miguel,Sciotti, Richard J.,Pecic, Stevan,D'Alessandro, Sarah,Taramelli, Donatella,?olaja, Bogdan A.
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supporting information
p. 264 - 281
(2016/01/29)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER
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The disclosures herein provide compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for non-invasive oral administration, invasive, intravenous, transdermal administration, or injection. Such compositions may be used to treatment of cancer and its metastasis or its associated complications.
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Paragraph 00187; 00188
(2013/03/26)
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- Reduction of Heterocycles with Nickel-Aluminum Alloy
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Pyrazines, pyridazines, isoxazoles, oxazole, 4-methylpyrimidine, and indole are reduced by nickel-aluminum alloy in potassium hydroxide solution.The reaction is simple to carry out and does not require special apparatus or hydrogen atmospheres.The products were the fully hydrogenated species although benzene rings were not attacked. 4-Methylpyrimidine gave 1,3-diaminobutane and oxazole gave 2-(methylamino)ethanol.It was found that the reaction frequently exhibited an induction period.
- Lunn, George
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p. 1043 - 1046
(2007/10/02)
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