- Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies
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A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity. Quinoline derivatives 3f and 3g were identified as potent hDHODH inhibitors while 3k and 3l demonstrated high cytotoxic activity against MCF-7 and A375 cells and good selectivity. In addition, the logD7.4 values obtained by the experimental method were found to be in the range from ?1.15 to 1.69. The chemical structures of all compounds were confirmed by IR, NMR and elemental analysis. The compounds pharmacology on the molecular level was revealed by means of molecular docking, highlighting the structural differences that distinguish highly active from medium and low active hDHODH inhibitors.
- Petrovi?, Milena M.,Roschger, Cornelia,Chaudary, Sidrah,Zierer, Andreas,Mladenovi?, Milan,Jakovljevi?, Katarina,Markovi?, Violeta,Botta, Bruno,Joksovi?, Milan D.
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- Studies on synthesis and structure-activity relationship (SAR) of derivatives of a new natural product from marine fungi as inhibitors of influenza virus neuraminidase
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Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy)-4-hydroxybenzaldehyde) exhibited the most potent inhibitory activity, with IC50 values of 26.96 μM for A/GuangdongSB/01/2009 (H1N1), 27.73 μM for A/Guangdong/03/2009 (H1N1), and 25.13 μM for A/Guangdong/05/2009 (H1N1), respectively, which is stronger than the benzoic acid derivatives (~mM level). These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA) inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR) analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification.
- Li, Jing,Zhang, Dingmei,Zhu, Xun,He, Zhenjian,Liu, Shu,Li, Mengfeng,Pang, Jiyan,Lin, Yongcheng
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experimental part
p. 1887 - 1901
(2011/12/04)
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- Preparation, crystal structure, and solid-state fluorescence of a CH 2Cl2-solvated crystal of 6,13-bis(t-butylphenyl)-2,3,9,10- tetrapropoxypentaeene
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Slow evaporation of 6,13-bis(t-butylphenyl)-2,3,9,10-tetrapropoxypentacene in CH2Cl2 solution in the dark, yielded CH 2Cl2-solvated single crystals easily. The crystals were characterized by X-ray analysis and solid-state fluorescence. Copyright
- Kitamura, Chitoshi,Naito, Takao,Yoneda, Akio,Kobayashi, Takashi,Naito, Hiroyoshi,Komatsu, Toshiki
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supporting information; scheme or table
p. 600 - 601
(2011/04/21)
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- 2,4-Diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase
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This paper describes the synthesis of 4′-substituted and 3′,4′-disubstituted 5-benzyl-2,4-diaminopyrimidines as selective inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Compounds were then assayed against the recombinant parasite and human enzymes. Some of the compounds showed good activity. They were also tested against the intact parasites using in vitro assays. Good activity was found against Trypanosoma cruzi, moderate activity against Trypanosoma brucei and Leishmania donovani. Molecular modeling was undertaken to explain the results. The leishmanial enzyme was found to have a more extensive lipophilic binding region in the active site than the human enzyme. Compounds which bound within the pocket showed the highest selectivity.
- Pez, Didier,Leal, Isabel,Zuccotto, Fabio,Boussard, Cyrille,Brun, Reto,Croft, Simon L.,Yardley, Vanessa,Ruiz Perez, Luis M.,Gonzalez Pacanowska, Dolores,Gilbert, Ian H.
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p. 4693 - 4711
(2007/10/03)
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- Cyclic compounds and uses thereof
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Compounds of general formula (1) R1—X1—W—X2—Z1—Z2—R2 or salts thereof, exhibiting preventive and therapeutic effects against HIV infectious diseases wherein R1is an optionally substituted five- or six-membered ring group; X1is a free valency or the like; W is a divalent group represented by, e. g., general formula (2) (wherein A and B are each an optionally substituted five- to seven-membered ring; E1and E4are each optionally substituted carbon or the like; E2and E3are each oxygen or the like; and a and b are each a single bond or a double bond); X2is a divalent group constituting a straight chain moiety; Z1is a divalent cyclic group or the like; Z2is a free valency or the like; and R2is optionally substituted amino or the like.
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- CYCLIC COMPOUNDS AND USES THEREOF
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Compounds of general formula (1) or salts thereof, exhibiting preventive and therapeutic effects against HIV infectious diseases wherein R1 is an optionally substituted five- or six-membered ring group; X1 is a free valency or the like; W is a divalent group represented by, e. g., general formula (2) (wherein A and B are each an optionally substituted five-to seven-membered ring; E1 and E4 are each optionally substituted carbon or the like; E2 and E3 are each oxygen or the like; and a and b are each a single bond or a double bond); X2 is a divalent group constituting a straight chain moiety; Z1 is a divalent cyclic group or the like; Z2 is a free valency or the like; and R2 is optionally substituted amino or the like.
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- Liquid-crystalline complexes of palladium(II) and platinum(II) with di- and tri-alkoxystilbazoles: Ligand control of mesomorphism
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Liquid-crystalline complexes of palladium and platinum are formed when the metals are complexed to stilbazoles (4-styrylpyridines) bearing either two or three alkoxy chains. The complexes, termed polycatenar, show smectic C mesophases for most 3,4-disubstituted ligands, while the use of trisubstituted ligands leads to complexes showing columnar organisation, demonstrating that the spatial organisation of the metals in the liquid-crystal mesophase can be rather readily controlled. Complexes of these di- and tri-substituted stilbazoles with a cis-dicarbonylchloroiridium(I) fragment were not liquid crystalline.
- Donnio, Bertrand,Bruce, Duncan W.
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p. 2745 - 2755
(2007/10/03)
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- Naphthalene derivatives and composition and methods of use, and aldehyde intermediates
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Naphthalene derivative of the formula: STR1 wherein R1 is hydrogen atom or a lower alkoxycarbonyl and R2 is a lower alkoxycarbonyl, or R1 and R2 are combined together to form a group of the formula: STR2 each of
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- Nitrogen containing heterocyclic compounds
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Compounds of the formula (III): STR1 or salts or acyl derivatives thereof, for use as antifungal and antiprotozoal agents are disclosed. Compositions containing the compounds are also disclosed as are method for the preparation of the compounds and interm
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- Alkoxynaphthalene derivatives
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Naphthalene derivative of the formula: STR1 wherein R1 is hydrogen atom or a lower alkoxycarbonyl and R2 is a lower alkoxycarbonyl, or R1 and R2 are combined together to form a group of the formula: STR2 each of
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