scholarly journals Trimethoprim: An Old Antibacterial Drug as a Template to Search for New Targets. Synthesis, Biological Activity and Molecular Modeling Study of Novel Trimethoprim Analogs

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 116 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Dawid Maliszewski ◽  
Maciej Baradyn ◽  
Danuta Drozdowska
Keyword(s):  
Dna Binding ◽  
Dihydrofolate Reductase ◽  
Binding Capacity ◽  
Antibacterial Drug ◽  
Inhibition Assay ◽  
Amide Bonds ◽  
Calf Thymus ◽  
A Minor ◽  
New Compounds

A new series of trimethoprim (TMP) analogs containing amide bonds (1–6) have been synthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were used to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium displacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA binding in a minor groove as well as determination of the association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT)2 and poly (dG-dC)2. Additionally, the mechanism of action of the new compounds was studied. In conclusion, some of our new analogs inhibited DHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into the analogs of TMP increases their affinity towards DHFR.

scholarly journals Synthesis, Biological Activity, and Molecular Dynamics Study of Novel Series of a Trimethoprim Analogs as Multi-Targeted Compounds: Dihydrofolate Reductase (DHFR) Inhibitors and DNA-Binding Agents

2021 ◽  
Vol 22 (7) ◽  
pp. 3685
Author(s):  
Agnieszka Wróbel ◽  
Maciej Baradyn ◽  
Artur Ratkiewicz ◽  
Danuta Drozdowska
Keyword(s):  
Dna Binding ◽  
Dihydrofolate Reductase ◽  
Solid Phase ◽  
Binding Capacity ◽  
Minor Groove ◽  
Amide Bond ◽  
Amide Bonds ◽  
Binding Agents ◽  
Pbr322 Plasmid ◽  
A Minor

Eighteen previously undescribed trimethoprim (TMP) analogs containing amide bonds (1–18) were synthesized and compared with TMP, methotrexate (MTX), and netropsin (NT). These compounds were designed as potential minor groove binding agents (MGBAs) and inhibitors of human dihydrofolate reductase (hDHFR). The all-new derivatives were obtained via solid phase synthesis using 4-nitrophenyl Wang resin. Data from the ethidium displacement test confirmed their DNA-binding capacity. Compounds 13–14 (49.89% and 43.85%) and 17–18 (41.68% and 42.99%) showed a higher binding affinity to pBR322 plasmid than NT. The possibility of binding in a minor groove as well as determination of association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT)2, and poly (dG-dC)2. With the exception of compounds 9 (IC50 = 56.05 µM) and 11 (IC50 = 55.32 µM), all of the compounds showed better inhibitory properties against hDHFR than standard, which confirms that the addition of the amide bond into the TMP structures increases affinity towards hDHFR. Derivatives 2, 6, 13, 14, and 16 were found to be the most potent hDHFR inhibitors. This molecular modelling study shows that they interact strongly with a catalytically important residue Glu-30.

Determination of the DNA binding properties of a novel PARP inhibitor MK-4827 with calf-thymus DNA by molecular simulations and detailed spectroscopic investigations

2019 ◽  
Vol 43 (17) ◽  
pp. 6702-6711 ◽  
Author(s):  
Hongqin Yang ◽  
Qingle Zeng ◽  
Ze He ◽  
Di Wu ◽  
Hui Li
Keyword(s):  
Dna Binding ◽  
Deoxyribonucleic Acid ◽  
Parp Inhibitor ◽  
Molecular Simulations ◽  
Binding Interaction ◽  
Binding Properties ◽  
Calf Thymus ◽  
Polymerase Inhibitor ◽  
Dna Binding Properties

The binding interaction of niraparib (MK-4827), a poly(ADP-ribose) polymerase inhibitor, with calf thymus deoxyribonucleic acid (ctDNA) has been explored by various theoretical and experimental techniques.

Studies of Australian Soft Corals. XLII. Structure Determination of New Briaran Derivatives From Briareum steckei (Coelenterata, Octocorallia, Gorgonacea)

1987 ◽  
Vol 40 (12) ◽  
pp. 2085 ◽  
Author(s):  
BF Bowden ◽  
JC Coll ◽  
W Patalinghug ◽  
BW Skelton ◽  
I Vasilescu ◽  
...  
Keyword(s):  
Single Crystal ◽  
High Field ◽  
Soft Corals ◽  
X Ray ◽  
Relative Stereochemistry ◽  
Minor Metabolite ◽  
A Minor ◽  
New Compounds ◽  
New Metabolites

The structure and relative stereochemistry of four new metabolites from Briareum steckei has been deduced from 2D-n.m.r. experiments at high field, and confirmed by a single-crystal X-ray determination of a minor metabolite. The new compounds are non-halogenated briaran derivatives: (1R*,2S*,3R*,5Z,7S*,8(17)Z,l0R*, llR *,12S*,14S*)- 3,14-diacetoxy- 11,12-epoxy- 18-oxobriara-5,8(17)-dien-2-yl butanoate (3), its 3-deacetoxy derivative (4), (1R*,2R*,4R*,5Z,7S*,8(17)Z,10R*, 11R *,12S*,14S*)-4,14-diacetoxy-11,12-epoxy-18-oxobriara-5,8(17)-dien-2-yl butanoate (5) and the related 2-propanoate (6). Single-crystal X-ray determinations were performed on (5) and (6).

Ce(IV)-mediated formation of benzenediazonium ion from a non-aminoazo dye, 1-phenylazo-2-hydroxy-naphthalene (Sudan I) and its binding to DNA

1989 ◽  
Vol 54 (7) ◽  
pp. 2021-2026
Author(s):  
Marie Stiborová ◽  
Befekadu Asfaw ◽  
Pavel Anzenbacher
Keyword(s):  
Azo Dyes ◽  
Acidic Medium ◽  
Model System ◽  
Calf Thymus Dna ◽  
Suitable Model ◽  
Principal Product ◽  
Calf Thymus ◽  
Sudan I ◽  
A Minor

Ce(IV) ions in acidic medium convert a carcinogenic non-aminoazo dye, 1-phenylazo-2-hydroxy-naphthalene (Sudan I) into an ultimate carcinogen, which binds to calf thymus DNA. The principal product of Sudan I oxidation by the Ce(IV) system is the benzenediazonium ion. A minor product is the dihydroxyderivative of Sudan I, 1-(4-hydroxyphenylazo)-2,6-dihydroxynaphthalene. Other minor coloured products (yellow and brown) were not identified. The principal product (the benzenediazonium ion) is responsible for the carcinogenicity of Sudan I, as it covalently binds to DNA. Ce(IV) ions in acidic medium represent a suitable model system, which imitates the activation route of carcinogenic azo dyes.

scholarly journals Reaktive E=C(p–p)π Systeme, XXXIV Addition von Alkoholen oder primären Aminen an Phosphaalkene F3CP=C(F)OR. Neue Trifluormethylphosphane und -phosphaalkene/Reactive E = C( p – p ) π-Systems, XXXIV Addition of Alcohols or Primary Amines to Phosphaalkenes F3CP= C(F)OR . Novel Trifluoromethylphosphanes and Phosphaalkenes

1993 ◽  
Vol 48 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Joseph Grobe ◽  
Duc Le Van ◽  
Gudrun Lange
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Molar Ratio ◽  
Primary Amines ◽  
The Novel ◽  
Experimental Conditions ◽  
Pull System ◽  
Fragment Ions ◽  
New Compounds ◽  
C Nmr

The course of the reactions o f fluorophosphaalkenes F3CP = C (F)OR [R = Me (1), Et (2)] with methanol or ethanol strongly depends on the experimental conditions. Thus at 70 °C a mixture of the 2-phosphapropionic acid ester F3CP (H )CO2R [R = Me (3), Et (4)] and trifluoromethylphosphane H2PCF3 is formed [molar ratio: 3 or 4 /H2 CF3 ≈1/1]. If the precursors F3CP (H )CO2R [R = Me (3), Et) are used as starting materials, the reaction with ROH under the same conditions affords 3 and 4, respectively, (90 to 95% yield) with only traces of H2PCF 3. In the presence o f iPr2NH these precursors react with R′OH to give the novel trifluoromethylphosphaalkenes F3CP = C (OR )OR [R /R′: Me/Me (6); E t/E t (7); Me/Et (8)]. With Et2NH , 3 undergoes an addition/elimination process yielding the interesting push/pull system Et2N(F)C = P-CO2Me (5). 1 and 2 react with primary amines R′NH2 (R′= tBu, Me) with stereoselective formation of the fairly labile phosphaalkenes F3CP = C(OR)NHR′ [R /R′: Me/tBu (9), Et/tBu(10), Me/Me (11)] with trans-positions for CF3 and NHR′.The new compounds 3 -11 were characterized by spectroscopic investigations (1H , 19F, 31P, 13C NMR ; IR, MS) and determination of M+ or typical fragment ions [M+ -OR ] by high resolution mass spectrometry.

DNA binding interaction studies of flavonoid complexes of Cu(II) and Fe(II) and determination of their chemotherapeutic potential

2019 ◽  
Vol 496 ◽  
pp. 119048
Author(s):  
Erum Jabeen ◽  
Naveed Kausar Janjua ◽  
Safeer Ahmed ◽  
Iftikhar Tahiri ◽  
Muhammad Kashif ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Interaction ◽  
Interaction Studies

Two lithium tricyanomethanide compounds: syntheses and single-crystal structure determination of LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO

2015 ◽  
Vol 70 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Olaf Reckeweg ◽  
Francis J. DiSalvo
Keyword(s):  
Crystal Structure ◽  
Single Crystal ◽  
Single Crystals ◽  
Structure Determination ◽  
Monoclinic Space Group ◽  
Orthorhombic Space Group ◽  
Space Group ◽  
Cell Parameters ◽  
New Compounds

AbstractThe new compounds LiK[C(CN)3]2 and Li[C(CN)3]·½ (H3C)2CO were synthesized and their crystal structures were determined. Li[C(CN)3]·½ (H3C)2CO crystallizes in the orthorhombic space group Ima2 (no. 46) with the cell parameters a=794.97(14), b=1165.1(2) and c=1485.4(3) pm, while LiK[C(CN)3]2 adopts the monoclinic space group P21/c (no. 14) with the cell parameters a=1265.7(2), b=1068.0(2) and c=778.36(12) pm and the angle β=95.775(7)°. Single crystals of K[C(CN)3] were also acquired, and the crystal structure was refined more precisely than before corroborating earlier results.

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