scholarly journals Dihydroquinazolines as a Novel Class of Trypanosoma brucei Trypanothione Reductase Inhibitors: Discovery, Synthesis, and Characterization of their Binding Mode by Protein Crystallography

2011 ◽  
Vol 54 (19) ◽  
pp. 6514-6530 ◽  
Author(s):  
Stephen Patterson ◽  
Magnus S. Alphey ◽  
Deuan C. Jones ◽  
Emma J. Shanks ◽  
Ian P. Street ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Protein Crystallography ◽  
Binding Mode ◽  
Synthesis And Characterization ◽  
Trypanothione Reductase ◽  
Reductase Inhibitors

High-resolution crystal structure of Trypanosoma brucei pteridine reductase 1 in complex with an innovative tricyclic-based inhibitor

2020 ◽  
Vol 76 (6) ◽  
pp. 558-564
Author(s):  
Giacomo Landi ◽  
Pasquale Linciano ◽  
Giusy Tassone ◽  
Maria Paola Costi ◽  
Stefano Mangani ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Neglected Tropical Diseases ◽  
Protozoan Parasite ◽  
Binding Mode ◽  
New Class ◽  
Hydrogen Bond Interactions ◽  
Promising Strategy ◽  
Trypanosomatid Parasites ◽  
Micromolar Range

The protozoan parasite Trypanosoma brucei is the etiological agent of human African trypanosomiasis (HAT). HAT, together with other neglected tropical diseases, causes serious health and economic issues, especially in tropical and subtropical areas. The classical antifolates targeting dihydrofolate reductase (DHFR) are ineffective towards trypanosomatid parasites owing to a metabolic bypass by the expression of pteridine reductase 1 (PTR1). The combined inhibition of PTR1 and DHFR activities in Trypanosoma parasites represents a promising strategy for the development of new effective treatments for HAT. To date, only monocyclic and bicyclic aromatic systems have been proposed as inhibitors of T. brucei PTR1 (TbPTR1); nevertheless, the size of the catalytic cavity allows the accommodation of expanded molecular cores. Here, an innovative tricyclic-based compound has been explored as a TbPTR1-targeting molecule and its potential application for the development of a new class of PTR1 inhibitors has been evaluated. 2,4-Diaminopyrimido[4,5-b]indol-6-ol (1) was designed and synthesized, and was found to be effective in blocking TbPTR1 activity, with a K i in the low-micromolar range. The binding mode of 1 was clarified through the structural characterization of its ternary complex with TbPTR1 and the cofactor NADP(H), which was determined to 1.30 Å resolution. The compound adopts a substrate-like orientation inside the cavity that maximizes the binding contributions of hydrophobic and hydrogen-bond interactions. The binding mode of 1 was compared with those of previously reported bicyclic inhibitors, providing new insights for the design of innovative tricyclic-based molecules targeting TbPTR1.

scholarly journals Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

2012 ◽  
Vol 8 ◽  
pp. 967-976 ◽  
Author(s):  
Marco Caricato ◽  
Nerea Jordana Leza ◽  
Claudia Gargiulli ◽  
Giuseppe Gattuso ◽  
Daniele Dondi ◽  
...  
Keyword(s):  
Functional Groups ◽  
Anion Recognition ◽  
Binding Mode ◽  
Optically Active ◽  
Synthesis And Characterization ◽  
Binding Affinities ◽  
One Pot ◽  
Axially Chiral ◽  
Diaryl Amines

We report on the synthesis and characterization of novel shape-persistent, optically active arylamide macrocycles, which can be obtained using a one-pot methodology. Resolved, axially chiral binol scaffolds, which incorporate either methoxy or acetoxy functionalities in the 2,2' positions and carboxylic functionalities in the external 3,3' positions, were used as the source of chirality. Two of these binaphthyls are joined through amidation reactions using rigid diaryl amines of differing shapes, to give homochiral tetraamidic macrocycles. The recognition properties of these supramolecular receptors have been analyzed, and the results indicate a modulation of binding affinities towards dicarboxylate anions, with a drastic change of binding mode depending on the steric and electronic features of the functional groups in the 2,2' positions.

Synthesis and characterization of new potent TLR7 antagonists based on analysis of the binding mode using biomolecular simulations

2021 ◽  
Vol 210 ◽  
pp. 112978
Author(s):  
Sourav Pal ◽  
Barnali Paul ◽  
Purbita Bandopadhyay ◽  
Nagothy Preethy ◽  
Dipika Sarkar ◽  
...  
Keyword(s):  
Binding Mode ◽  
Synthesis And Characterization ◽  
Biomolecular Simulations

Oxazoline chemistry. Part VIII. Synthesis and characterization of a new class of pincer ligands derived from the 2-(o-anilinyl)-2-oxazoline skeleton — Applications to the synthesis of group X transition metal catalysts

2005 ◽  
Vol 83 (8) ◽  
pp. 1185-1189 ◽  
Author(s):  
Andreas Decken ◽  
Robert A Gossage ◽  
Paras N Yadav
Keyword(s):  
Heck Reaction ◽  
Picolinic Acid ◽  
Point Group ◽  
Binding Mode ◽  
Transition Metal Catalysts ◽  
Synthesis And Characterization ◽  
Pincer Ligands ◽  
Bond Forming ◽  
Pd Complexes

The synthesis and characterization of a new and readily synthesized class of potentially anionic pincer ligands with C1 point group symmetries is described. These materials can be made via amide coupling of a 2-(2′-anilinyl)-2-oxazoline unit with picolinic acid; the incorporation of enantiopure oxazoline fragments facilitates the construction of chiral C1 pincers. Treatment of the free ligands with Pd metal sources leads to the formation of amido–Pd pincer complexes in good yield. One of these Pd complexes has been characterized by single crystal X-ray diffraction methods, which confirms the proposed tridentate binding mode of the ligand and the formation of an amido N—Pd bond. The metal complexes have been shown to be suitable precusors for catalytically active Pd species that are useful for C—C bond forming reactions, notably the Heck reaction under standard conditions. Key words: oxazoline, 4,5-dihydro-2-oxazole, palladium, pincer ligand, amido, Heck reaction.

scholarly journals Synthesis and Characterization of Zinc (II) Phthalocyanine for Screening Potential Solar Cell Dye Application

2022 ◽  
Vol 9 (1) ◽  
pp. 3-10
Author(s):  
Connor Atkinson
Keyword(s):  
Dye Sensitized Solar Cells ◽  
Soret Band ◽  
Binding Mode ◽  
Base Catalysis ◽  
Synthesis And Characterization ◽  
Solar Concentrators ◽  
Dye Sensitized ◽  
Luminescent Solar Concentrators ◽  
Sensitized Solar Cells

Phthalocyanine molecules have the potential to be used in select Dye Sensitized Solar Cells (DSSCs) and Luminescent Solar Concentrators (LSCs), due to UV-Vis absorbance in the 300-450 (nm) Soret Band, corresponding to π HOMO-1 to π* LUMO transition and 550-690 (nm) Q-band, corresponding to π HOMO to π* LUMO transitions. In this study Tetranitro Zinc (II) Phthalocyanine is synthesized via base catalysis before the product is characterized via IR, 1H NMR & UV-Vis analysis. Assessing the desirability of the Tetranitro Zinc (II) Phthalocyanine as a solar organic semiconducting dye in DSSCs and LSCs. The desirability is assessed by novel computational DFT calculations, of the aggregation binding mode to deduce if Aggregation-Caused Quenching (ACQ) is occurring in the aggregated sample. ACQ is known to reduce DSSCs and LSCs generation of useful photo-active current. Aggregation-Caused Quenching (ACQ) is mathematically indicated in Phthalocyanine aggregation and Tetranitro Zinc (II) Phthalocyanine’s desirability is assessed for further use in DSSCs and LSCs.

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