Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase

Metal-Catalyzed Intramolecular Hydrolysis of Phosphate Esters

A tridentate water-soluble phosphotriester ligand has been synthesized. Kinetics studies have shown that divalent metal ions dramatically enhance the rate of hydrolysis of such phosphotriester at 25 °C and pH 8.0 via intramolecular nucleophilic attack by a metal bound hydroxide

Catalysis by Supported Lewis Acids: An Efficient Method for Transesterification of Phosphotriesters

Lewis acids (ZnCl2, CoCl2, NiCl2, TiCl4, and CdCl2) when supported on silica gel can effectively catalyze transesterification of organophosphotriesters. In anhydrous acetonitrile and in the presence of excess alcohol, such reactions follow pseudo-first-order kinetics. Progress and efficacy of these reactions were monitored by UV-vis and 31P NMR spectroscopy

Synthesis of Iron-Binding Oligonucleotides and Their Reactions With Single-Stranded DNA

Two 12-base oligonucleotides were synthesized and modified by attaching metal-binding ligands (2,6-pyridinedicarboxylate and 2,2′-dipicolylamine) to their 5′-ends. When hybridized to a 135-base single stranded DNA, in the presence of Fe2+, O2, and a reducing agent, these obligonucleotides cleaved the complementary DNA chain with unique and high base-sequence specificities

Sequence-Specific Cleavage of DNA by Oligonucleotide-Bound Metal Complexes

2,6-Dicarboxypyridine (DCP) and N,N-bis(2-picolyl)amine (DPA) ligands were synthesized and attached via ethylene groups to the 5′-ends of 12-base oligonucleotides. The base-sequence of the oligonucleotide probes were chosen to be 5′-T-C-G-C-C-T-T-G-C-A-G-C-3′, which is complementary to a 12-base sequence in pUC9 plasmid DNA. When hybridized to a denatured BamHI/PvuI restriction fragment of pUC9 in the presence of Fe2+, oxygen, and a reducing agent, these probes afforded specific cleavage at their complementary sequences in the 135-base-pair template. Analysis of the cleavage fragments by high-resolution polyacrylamide gel electrophoresis indicated that both probes cleaved DNA at a single stretch of bases near the position of the tethered ligand. The cleaving activity of DPA-12-mer was unusually high and extended over eight contiguous nucleotides. DCP-12-mer showed an unprecedented high cleavage specificity extending over two nucleotides only

Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth.

We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase

Metal Complexes of Modified Cyclen as Catalysts for Hydrolytic Restriction of Plasmid DNA

Simple and novel nuclease models have been synthesized. These involve metal-binding ligand 1,4,7,10-tetraazlcyclododecane (cyclen) tethered to an acridine ring (a DNA-binding group) by amide linkers of various lengths. Binding of these probes to DNA was studied by monitoring changes in their UV-visible spectra affected by the presence of DNA. Titration of these compounds with increasing amounts of pBR322 DNA caused hypochromic effects and shifted the acridine absorption at 360nm to a longer wavelength. Under biologically relevant conditions (37°C and pH 7.4), specific transition metal complexes of these compounds are found to be highly effective catalysts toward the hydrolysis of plasmid DNA. This is demonstrated by their ability to convert the super-coiled DNA (form I) to open-circular DNA (form II). Structure-activity correlation studies show that hydrolytic activity depends on both the structure of ligand (L1\u3eL2\u3eL3) and the nature of metal ion cofactor (Co3+\u3eZn2+\u3eCr2+\u3eNi2+\u3eCu2+\u3eFe3+)

Hydrolysis of Phosphotriesters Promoted by a Zinc(II) Complex Bearing an Alcohol Pendant

A polyamine-zinc(II) complex with an alcohol pendant promotes the hydrolysis of diethyl(4-nitrophenyl)phosphate via transfer of the diethylphosphate group to its alkoxy pendant