Olga Burchak - Academia.edu (original) (raw)

Papers by Olga Burchak

Journal of Antimicrobial Chemotherapy, 2015

We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtain... more We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtained during the development of new ways of synthesis of marine bis-indole alkaloids from the spongotine, topsentin and hamacanthin classes. Innovative ways of synthesis and further structural optimizations led to bis-indoles presenting either the 1-(1H-indol-3'-yl)-1,2-diaminoethane unit or the 1-(1H-indol-3-yl)ethanamine unit. MIC determination was performed for reference and clinical strains of Staphylococcus aureus and CoNS species. MBC, time-kill kinetics, solubility, hydrophobicity index, plasma protein-binding and cytotoxicity assays were performed for lead compounds. Inhibition of the S. aureus NorA efflux pump was also tested for bis-indoles with no antistaphylococcal activity. Lead compounds were active against both S. aureus and CoNS species, with MICs between 1 and 4 mg/L. Importantly, the same MICs were found for MRSA and vancomycin-intermediate S. aureus strains. Early concentration-dependent bactericidal activity was observed for lead derivatives. Compounds with no intrinsic antibacterial activity could inhibit the S. aureus NorA efflux pump, which is involved in resistance to fluoroquinolones. At 0.5 mg/L, the most effective compound led to an 8-fold reduction of the ciprofloxacin MIC for the SA-1199B S. aureus strain, which overexpresses NorA. However, the bis-indole compounds displayed a high hydrophobicity index and high plasma protein binding, which significantly reduced antibacterial activity. We have synthesized and characterized novel bis-indole derivatives as promising candidates for the development of new antistaphylococcal treatments, with preserved activity against MDR S. aureus strains.

ChemInform, 2009

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synlett, 2010

ABSTRACT Three new alpha-cyclopropyl nitrones have been synthesized as mechanistic probes for red... more ABSTRACT Three new alpha-cyclopropyl nitrones have been synthesized as mechanistic probes for reductive cross-coupling reactions of nitrones. The alpha-cyclopropylcarbinyl radical intermediate formed by single electron transfer from SmI2 to these nitrones is not prone to ring opening, due to a unique stabilization by the vicinal N-O-Sm system. Consequently, beta-cyclopropyl hydroxylamines could be prepared in high yield from alpha-cyclopropyl nitrones.

Organic Letters, 2008

Various alpha,alpha-disubstituted 2-pyrrolidinylmethanols are efficiently prepared in a single st... more Various alpha,alpha-disubstituted 2-pyrrolidinylmethanols are efficiently prepared in a single step from ketones using a SmI2-mediated cross-coupling with 1-pyrroline N-oxide. The N-hydroxy-alpha,alpha-diphenylprolinol is also easily prepared and resolved.

Journal of the American Chemical Society, 2011

Fluorescence imaging in clinical diagnostics and biomedical research relies to a great extent on ... more Fluorescence imaging in clinical diagnostics and biomedical research relies to a great extent on the use of small organic fluorescent probes. Because of the difficulty of combining fluorescent and molecular-recognition properties, the development of such probes has been severely restricted to a number of well-known fluorescent scaffolds. Here we demonstrate that autofluorescing druglike molecules are a valuable source of bioimaging probes. Combinatorial synthesis and screening of chemical libraries in droplet microarrays allowed the identification of new types of fluorophores. Their concise and clean assembly by a multicomponent reaction presents a unique potential for the one-step synthesis of thousands of structurally diverse fluorescent molecules. Because they are based upon a druglike scaffold, these fluorophores retain their molecular recognition potential and can be used to design specific imaging probes.

ChemBioChem, 2006

ABSTRACT Probing an alternative route. Ubiquitin and Ub-like proteins (Ubl) are attached to cellu... more ABSTRACT Probing an alternative route. Ubiquitin and Ub-like proteins (Ubl) are attached to cellular proteins through a conserved conjugation pathway. We demonstrate here that Ub and Ubl thioesters, the key intermediates of this pathway, can be readily transferred onto cysteine-containing artificial substrates. This finding provides new insight into the chemistry of Ub (Ubl) conjugation and can be used for creating different protein probes and microarrays.

Bioorganic & Medicinal Chemistry Letters, 2006

The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluoresce... more The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluorescein in three steps with common commercially available precursors, they all generate bright green fluorescence upon proteolysis. Their particular structure allows the same substrate be used to report enzymatic activity of various proteases from serine and cysteine superfamilies. The substrate cleavage is sensitive to specific protease inhibitors providing a tool for inhibitor screening. Figure 1. Schematic representation of fluorogenic ester substrates and protease cleaved product.

Bioorganic & Medicinal Chemistry, 2011

A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indo... more A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indoles to nitrones. The compounds were then tested for their antibacterial activity against almost thirty bacterial strains representative of common human pathogens. Two types of indolic molecules inhibit the growth of Staphylococcus aureus, including MRSA and VISA strains, with MIC values ranging from 8 to 16 mg/L.

Bioorganic & Medicinal Chemistry, 2006

An efficient synthesis of new type fluorescent amino acids is described. The Fmoc-protected dyes ... more An efficient synthesis of new type fluorescent amino acids is described. The Fmoc-protected dyes can be prepared in a four-step procedure with 3030% overall yield from aminofluoresceins and other inexpensive commercially available precursors. The dyes are much more photostable compared to fluorescein and exhibit constant pH-independent fluorescence that is advantageous in biological applications. The Fmoc-protected fluorescent amino acids are ready for use in solid phase peptide synthesis. As a proof of concept, a fluorogenic papain substrate was synthesized and employed for on-bead detection of the protease activity. By using a novel technique for quantitative analysis of bead fluorescence, a 302.7-fold increase in mean bead brightness was measured and was attributed to substrate cleavage by papain. The new type fluorescent amino acids seem to be a promising tool for the synthesis of fluorescent peptide ligands and fluorogenic protease substrates.

Angewandte Chemie International Edition, 2009

Angewandte Chemie International Edition, 2009

Chemical Physics, 2012

Linear-response time-dependent (TD) density-functional theory (DFT) has been implemented in the p... more Linear-response time-dependent (TD) density-functional theory (DFT) has been implemented in the pseudopotential wavelet-based electronic structure program BigDFT and results are compared against those obtained with the all-electron Gaussian-type orbital program deMon2k for the calculation of electronic absorption spectra of N2 using the TD local density approximation (LDA). The two programs give comparable excitation energies and absorption spectra once suitably extensive basis sets are used. Convergence of LDA density orbitals and orbital energies to the basis-set limit is significantly faster for BigDFT than for deMon2k. However the number of virtual orbitals used in TD-DFT calculations is a parameter in BigDFT, while all virtual orbitals are included in TD-DFT calculations in deMon2k. As a reality check, we report the x-ray crystal structure and the measured and calculated absorption spectrum (excitation energies and oscillator strengths) of the small organic molecule N -cyclohexyl-2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-amine.

Journal of Antimicrobial Chemotherapy, 2015

We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtain... more We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtained during the development of new ways of synthesis of marine bis-indole alkaloids from the spongotine, topsentin and hamacanthin classes. Innovative ways of synthesis and further structural optimizations led to bis-indoles presenting either the 1-(1H-indol-3'-yl)-1,2-diaminoethane unit or the 1-(1H-indol-3-yl)ethanamine unit. MIC determination was performed for reference and clinical strains of Staphylococcus aureus and CoNS species. MBC, time-kill kinetics, solubility, hydrophobicity index, plasma protein-binding and cytotoxicity assays were performed for lead compounds. Inhibition of the S. aureus NorA efflux pump was also tested for bis-indoles with no antistaphylococcal activity. Lead compounds were active against both S. aureus and CoNS species, with MICs between 1 and 4 mg/L. Importantly, the same MICs were found for MRSA and vancomycin-intermediate S. aureus strains. Early concentration-dependent bactericidal activity was observed for lead derivatives. Compounds with no intrinsic antibacterial activity could inhibit the S. aureus NorA efflux pump, which is involved in resistance to fluoroquinolones. At 0.5 mg/L, the most effective compound led to an 8-fold reduction of the ciprofloxacin MIC for the SA-1199B S. aureus strain, which overexpresses NorA. However, the bis-indole compounds displayed a high hydrophobicity index and high plasma protein binding, which significantly reduced antibacterial activity. We have synthesized and characterized novel bis-indole derivatives as promising candidates for the development of new antistaphylococcal treatments, with preserved activity against MDR S. aureus strains.

ChemInform, 2009

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synlett, 2010

ABSTRACT Three new alpha-cyclopropyl nitrones have been synthesized as mechanistic probes for red... more ABSTRACT Three new alpha-cyclopropyl nitrones have been synthesized as mechanistic probes for reductive cross-coupling reactions of nitrones. The alpha-cyclopropylcarbinyl radical intermediate formed by single electron transfer from SmI2 to these nitrones is not prone to ring opening, due to a unique stabilization by the vicinal N-O-Sm system. Consequently, beta-cyclopropyl hydroxylamines could be prepared in high yield from alpha-cyclopropyl nitrones.

Organic Letters, 2008

Various alpha,alpha-disubstituted 2-pyrrolidinylmethanols are efficiently prepared in a single st... more Various alpha,alpha-disubstituted 2-pyrrolidinylmethanols are efficiently prepared in a single step from ketones using a SmI2-mediated cross-coupling with 1-pyrroline N-oxide. The N-hydroxy-alpha,alpha-diphenylprolinol is also easily prepared and resolved.

Journal of the American Chemical Society, 2011

Fluorescence imaging in clinical diagnostics and biomedical research relies to a great extent on ... more Fluorescence imaging in clinical diagnostics and biomedical research relies to a great extent on the use of small organic fluorescent probes. Because of the difficulty of combining fluorescent and molecular-recognition properties, the development of such probes has been severely restricted to a number of well-known fluorescent scaffolds. Here we demonstrate that autofluorescing druglike molecules are a valuable source of bioimaging probes. Combinatorial synthesis and screening of chemical libraries in droplet microarrays allowed the identification of new types of fluorophores. Their concise and clean assembly by a multicomponent reaction presents a unique potential for the one-step synthesis of thousands of structurally diverse fluorescent molecules. Because they are based upon a druglike scaffold, these fluorophores retain their molecular recognition potential and can be used to design specific imaging probes.

ChemBioChem, 2006

ABSTRACT Probing an alternative route. Ubiquitin and Ub-like proteins (Ubl) are attached to cellu... more ABSTRACT Probing an alternative route. Ubiquitin and Ub-like proteins (Ubl) are attached to cellular proteins through a conserved conjugation pathway. We demonstrate here that Ub and Ubl thioesters, the key intermediates of this pathway, can be readily transferred onto cysteine-containing artificial substrates. This finding provides new insight into the chemistry of Ub (Ubl) conjugation and can be used for creating different protein probes and microarrays.

Bioorganic & Medicinal Chemistry Letters, 2006

The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluoresce... more The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluorescein in three steps with common commercially available precursors, they all generate bright green fluorescence upon proteolysis. Their particular structure allows the same substrate be used to report enzymatic activity of various proteases from serine and cysteine superfamilies. The substrate cleavage is sensitive to specific protease inhibitors providing a tool for inhibitor screening. Figure 1. Schematic representation of fluorogenic ester substrates and protease cleaved product.

Bioorganic & Medicinal Chemistry, 2011

A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indo... more A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indoles to nitrones. The compounds were then tested for their antibacterial activity against almost thirty bacterial strains representative of common human pathogens. Two types of indolic molecules inhibit the growth of Staphylococcus aureus, including MRSA and VISA strains, with MIC values ranging from 8 to 16 mg/L.

Bioorganic & Medicinal Chemistry, 2006

An efficient synthesis of new type fluorescent amino acids is described. The Fmoc-protected dyes ... more An efficient synthesis of new type fluorescent amino acids is described. The Fmoc-protected dyes can be prepared in a four-step procedure with 3030% overall yield from aminofluoresceins and other inexpensive commercially available precursors. The dyes are much more photostable compared to fluorescein and exhibit constant pH-independent fluorescence that is advantageous in biological applications. The Fmoc-protected fluorescent amino acids are ready for use in solid phase peptide synthesis. As a proof of concept, a fluorogenic papain substrate was synthesized and employed for on-bead detection of the protease activity. By using a novel technique for quantitative analysis of bead fluorescence, a 302.7-fold increase in mean bead brightness was measured and was attributed to substrate cleavage by papain. The new type fluorescent amino acids seem to be a promising tool for the synthesis of fluorescent peptide ligands and fluorogenic protease substrates.

Angewandte Chemie International Edition, 2009

Angewandte Chemie International Edition, 2009

Chemical Physics, 2012

Linear-response time-dependent (TD) density-functional theory (DFT) has been implemented in the p... more Linear-response time-dependent (TD) density-functional theory (DFT) has been implemented in the pseudopotential wavelet-based electronic structure program BigDFT and results are compared against those obtained with the all-electron Gaussian-type orbital program deMon2k for the calculation of electronic absorption spectra of N2 using the TD local density approximation (LDA). The two programs give comparable excitation energies and absorption spectra once suitably extensive basis sets are used. Convergence of LDA density orbitals and orbital energies to the basis-set limit is significantly faster for BigDFT than for deMon2k. However the number of virtual orbitals used in TD-DFT calculations is a parameter in BigDFT, while all virtual orbitals are included in TD-DFT calculations in deMon2k. As a reality check, we report the x-ray crystal structure and the measured and calculated absorption spectrum (excitation energies and oscillator strengths) of the small organic molecule N -cyclohexyl-2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-amine.