Agnieszka Bogusława Olejniczak

• Prof.
• Group Leader at Screening Laboratory Institute of Medical Biology PAS

Sulfonylureas (SUs)—a class of drugs primarily used to treat type 2 diabetes—have recently attracted interest for their potential anticancer properties. While some studies have explored the chemical modification or design of new SU derivatives, our work instead centers on biological evaluations of all commercially available SUs in combination with...

The presented study depicts the synthesis of 11 carborane–thiazole conjugates with anticancer activity, as well as an evaluation of their biological activity as inhibitors of two enzymes: tyrosinase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The overexpression of tyrosinase results in the intracellular accumulation of melanin and can b...

In this study, the structural attributes of nanoparticles obtained by a renewable and non-immunogenic “inulinated” analog of the “pegylated” PLA (PEG-PLA) were examined, together with the potential of these novel nanocarriers in delivering poorly water-soluble drugs. Characterization of INU-PLA assemblies, encompassing critical aggregation concentr...

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro...

Background Ovarian cancer is one of the most frequent and deadly gynaecological cancers, often resistant to platinum-based chemotherapy, the current standard of care. Halophilic microorganisms have been shown to produce a large variety of metabolites, some of which show toxicity to various cancer cell lines. However, none have yet been shown to be...

The study investigated the structure-activity relationship of newly synthesized dye-linker-macrocycle (DLM) conjugates and the effect of each component on various biological properties, including cytotoxicity, cellular uptake, intracellular localization, interaction with DNA and photodynamic effects. The conjugates were synthesized by combining 1,8...

2-Azabicycloalkanes: 2-azabicyclo[2.2.1]heptane and 2-azabicyclo[3.2.1]octane were used as a chiral platform for the construction of a set of 1,2,3-triazole, thiourea, and ebselen derivatives. Cytotoxicity and antiviral activity studies revealed the most promising potency for selected thioureas.

Synthesis of acridine derivatives that act as DNA‐targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carbor...

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding prop...

Chiral sulfonamides with aromatic fragments are important chemical building blocks found widely in many natural products, catalysts, and molecules of biological importance. In this report, we describe the efficient synthesis of a series of chiral sulfonamides which, in addition to the aromatic part (phenyl, biphenyl, and dansyl units), possess N-he...

Starting with fluorinated benzylamines, a series of 2-unsubstituted imidazole N-oxides was prepared and subsequently deoxygenated in order to prepare the corresponding imidazoles. The latter were treated with benzyl halides yielding imidazolium salts, which are considered fluorinated analogues of naturally occurring imidazolium alkaloids known as l...

In the present study, we continue our work related to the synthesis of 1,8-naphthalimide and carborane conjugates and the investigation of their anticancer activity and DNA-binding ability. For this purpose, a series of 4-carboranyl-1,8-naphthalimide derivatives, mitonafide, and pinafide analogs were synthesized using click chemistry, reductive ami...

Distinctive biological properties characterize 1,8-naphthalimides and their derivatives. This study presents and compares the activity of a series of compounds where 1,8-naphthalimide fragment was attached either to carborane or metallacarborane...

Nucleosides and their derivatives are a well-known and well-described class of compounds with antiviral activity. Currently, in the era of the COVID-19 pandemic, scientists are also looking for compounds not related to nucleosides with antiviral properties. This review aims to provide an overview of selected synthetic antiviral agents not associate...

In the current work, we present a broad analysis of cytotoxicity toward normal (kidney and lung) and cancer (lung, liver, and cervix) cells of ionic liquids (ILs) with imidazolium cations and cyano-based or bis(trifluoromethylsulfonyl)imide anions. Additionally, we verify if ILs might be candidates for new potential virucidal agents. We observed th...

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses show...

Tuberculosis (TB) is a severe infectious disease with high mortality and morbidity. The emergence of drug-resistant TB has increased the challenge to eliminate this disease. Isoniazid (INH) remains the key and effective component in the therapeutic regimen recommended by World Health Organization (WHO). A series of isoniazid-carborane derivatives c...

Carboranes are unusual compounds with unique structural and chemical properties, which play an increasingly important role in the design of new potential pharmaceuticals. One of the noteworthy properties of closo-carboranes is their very high hydrophobicity, which can facilitate transport of carborane-containing compounds across biological membrane...

We have recently found that selected thio-disaccharides possess bactericidal effects against Mycobacterium tuberculosis but not against Escherichia coli or Staphylococcus aureus. Here, we selected spontaneous mutants displaying resistance against the investigated thio-glycoside. According to next-generation sequencing, four of six analyzed mutants...

(1-4)-Thiodisaccharides, thiosugars with the 1-4-thio bridge, were recently shown to induce oxidative stress, as well as, apoptosis in cancer cells in the low micromolar range; however, the detailed mechanism of their anticancer action still remains unknown. In order to clarify the mechanism of (1-4)- thiodisaccharides action, we performed a series...

The development of 1,8-naphthalimide derivatives as DNA-targeting anticancer agents is a rapidly growing area and has resulted in several derivatives entering into clinical trials. One of original recent developments is the use of boron clusters: carboranes and metallacarboranes in the design of pharmacologically active molecules. In this direction...

Background: Nucleoside analogs are important class of chemotherapeutics. One of the original openings in the nucleoside medicinal chemistry was derivatives comprising a boron cluster component. Results: A series of adenosine derivative pairs containing inorganic boron cluster or alternatively its mimic, organic phenyl modification were synthesized...

Antimicrobial resistance (AMR) is an exceptional increasing challenge for human health; it is urgently need to develop novel leads that can be developed to clinically useful drugs. The idea to modify old class of antibiotics that has been a cornerstone of medical has been dramatically refreshed searching for ways to overcome antibiotic-resistant ba...

Together with tremendous progress in biotechnology, nucleic acids, while retaining their status as “molecules of life”, are becoming “molecular wires”, materials for the construction of molecular structures at the junction between the biological and abiotic worlds. Herein, we present an overview of the approaches for incorporating metal centers int...

The interaction of boron clusters, and especially ionic boron clusters, with water and molecular hosts is reviewed. As result, even the water‐soluble ionic boron clusters are found to thrive in both an aqueous and a non‐aqueous environment, making them neither purely hydrophilic nor purely hydrophobic. The boron clusters are therefore offering new...

We synthesized a series of new uridine and 2′-deoxyuridine conjugates of the o-carborane cluster attached at C-5 through a linker comprising the ethynyl group and/or triazole ring separated by alkane chains. The obtained conjugates have low or medium toxicity and are phosphorylated moderately by nucleoside kinases TK1 and TK2 and efficiently by dCK...

Lipophilicity was investigated for 20 2'-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D7.4) for...

5-[(p-Carborane-2-yl)ethynyl]-2'-deoxyuridine 5'-O-triphosphate was synthesized and used as a good substrate in enzymatic construction of carborane-modified DNA or oligonucleotides containing up to 21 carborane moieties in primer extension reactions by DNA polymerases.

The DNA ligases, enzymes that seal breaks in the backbones of DNA, are essential for all organisms, however bacterial ligases essential for DNA replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5′-triphosphate. This fact leads to the conclusion that NAD⁺-...

A series of adenosine derivatives bearing a boron cluster were synthesized and evaluated for their cytotoxicity against primary peripheral mononuclear cells from the blood of 17 patients with leukemias (16 CLL and 1 very rare PLL), as well as from 5 healthy donors used as a control. Among the tested agents, two, i.e., compounds 1 and 2, displayed h...

supplementary information New Journal of Chemistry 2015, 39, 1202-1221

We disclose nucleoside derivatives useful as drugs particularly for the treatment of chronic lymphoytic leukemia

Metallocarbonyl complexes display specific and intense absorption bands in the mid-IR spectral range due to the stretching vibrations of carbonyl ligands, which makes them useful labels for biocompounds. In the course of searching for new labelling methods for biomolecules, we attempted O-alkylation of various hydroxyl compounds. Methanol, selected...

A synthetic strategy for functionalization of the three vertices of o-carborane and the attachment of the obtained triped to the solid support was developed. Further functionalization of the triped with short DNA sequences by automated DNA synthesis was achieved. The proposed methodology is a first example of boron cluster chemistry on a solid supp...

A series of novel conjugates of para-carborane with 5-ethynyl-uridine or 2'-deoxyuridine were synthesized. The conjugates were prepared by Sonogashira coupling of para-carborane terminal alkynes and 5-iodo-nucleoside. The designed compounds demonstrated low to moderate cytotoxicity in several cell lines. The antiviral activities of the agents were...

This paper describes a general method for the synthesis of four canonical nucleosides T, dC, dA and dG and their phosphoramidites suitable for automated synthesis of DNA modified with a carborane cage. A boron cluster in the form of an electroneutral, lipophilic 1,2-dicarba-closo-dodecaborane (C2B9H11) or negatively charged, redox-active 7,8-dicarb...

Modified oligonucleotides are potential candidates for therapeutic nucleic acids technology and applications as tools in molecular biology. Despite broad use and extensive studies of the modified DNA/RNA-oligomers there is a continuous need to improve their properties. These properties, related mainly to migration through the cell membranes, resist...

A library of purine and pyrimidine nucleosides modified with carborane or metallacarborane boron clusters at different locations, consisting of new molecules as well as already described compounds, was prepared. The compounds were tested as substrates for human deoxynucleoside kinases. Some conjugates, with modification attached to N3 of thymidine...

In this work, we report on oligonucleotide probes bearing metallacarborane [3-iron bis(dicarbollide)] redox label, deposited on gold electrode for electrochemical determination of DNA sequence derived from Avian Influenza Virus (AIV), type H5N1. The oligonucleotide probes containing 5'-terminal NH2 group were covalently attached to the electrode, v...

Methods for the modification of ganciclovir (GCV), acyclovir (ACV), cidofovir (CDV) and valganciclovir (VCDV) with boron cluster have been developed. Toxicity of the new derivatives was evaluated in adherent cells; no cytotoxicity was observed in five different cell lines up to 1000 microM with the exception of modified valganciclovir which was cyt...

It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug. They are designed in order to improve the physicochemical, biop...

A method for the synthesis of cholesterol–metallacarborane conjugates bearing cobalt, iron and chromium was developed. Effective incorporation of the cholesterol conjugate bearing cobalt into liposome membrane was revealed. Using the metallacarborane-encrusted liposomes as boron delivery system in vivo biodistribution experiments in tumor-bearing m...

Synthesis of novel neuraminidase inhibitor -- carborane ester of oseltamivir carboxylic acid is described, and its physicochemical and spectral characteristics is provided. Surprisingly, carborane analog of oseltamivir is of an order of magnitude less active than its precursor, the corresponding ethyl ester, which is the active principle of pharmac...

Methods for the synthesis of adenosine/boron cluster conjugates are proposed and the potential of the obtained derivatives to modulate neutrophil activity, especially reactive oxygen species (ROS) production in vitro, is described. An efficient inhibition of ROS production in activated neutrophils by adenosine modified at the 2'-C and 6-N positions...

A new type of nucleoside-metallacarborane conjugate is presented. 3,3,3-Tricarbonyl-closo- 3,1,2-ReC2B9H10 is used as a modifying unit. The method is based on the de novo formation of a metallacarborane complex via the reaction of [NEt4]2[ReBr3(CO)3] with the uridine-bearing carborane as a boron cluster ligand. The uridine-tricarbonyl rhenacarboran...

The evaluation of novel electrochemically active label for electrochemical detection of DNA hybridization is presented. Metallacarborane units modified with iron, cobalt or chromium were investigated. The value of redox potential and relatively strong current signal facilitate usage of Fe-carborane as marker covalently attached to the ssDNA. In ele...

The present work reports the efficient synthesis of oligonucleotides bearing metallacarborane complexes containing iron (3,3-iron-1,2,1,2-dicarbollide) on a solid support via the H-phosphonate method. This versatile methodology can be applied to the synthesis of DNA oligomers bearing various metallacarborane units.

CONJUGATES OF PURINE AND PYRIMIDINE NUCLEOSIDES: thymidine and 2'-deoxyguanosine with cobalt-metallacarborane were studied for their sodium ion complexing properties. Formation of stable complexes of 1 : 1 stoichiometry was proved by ESI MS spectroscopy and (23)Na NMR. Equilibrium constants and energies of complex formation were calculated. Complex...

Novel types of adenosine and 2'-deoxyadenosine derivatives containing boron clusters at positions C2', N6, or C8 were synthesized. The effect of these modified compounds on platelet function was studied. Modification of adenosine at the C2' position with a para-carborane cluster (C(2)B(10)H(11)) results in efficient inhibition of platelet function,...

General methods for the synthesis of nucleosides modified with borane clusters and metallacarborane complexes are presented. These include: (1) the click chemistry approach based on Huisgen 1,3-dipolar cycloaddition and (2) tethering of the metallacarborane group to the aglycone of a nucleoside via a dioxane ring opening in oxonium metallacarborane...

Metallacarborane bearing chromium is proposed as the electrochemical label for electrochemical coding of DNA. Synthesis and HDV characteristics of 2′-deoxyadenosine (dA) containing [(3,3′-chromium-1,2,1′,2′-dicarbollide)](−1)]ate complex are described. The proposed labeling of nucleosides, together with previously described nucleoside/metallacarbor...

Polyhedral boron clusters are proposed as new, chemically and biologically stable, versatile redox labels for electrochemical DNA hybridization sensors. Selective and sensitive detection of the redox labeled DNA-probe was achieved by means of covalently attached electroactive marker 7,8-dicarba-nido-undekaborate group. A nanomolar concentration of...

We report the first evidence that boron-containing nucleoside conjugates have a tendency to associate in water solutions. The size, charge, and exoskeletal pattern of the boron cluster can strongly influence the aggregation. The aggregation of nucleosides with attached boron clusters was observed using light scattering and atomic force microscopy t...

The method was developed for the synthesis of biologically important adenosine phosphates, AMP, cAMP and ATP modified with p -carborane cluster - a highly lipophilic pharmacophore. The adenosine phosphates modified with p -carborane are characterized by increased stability in human blood plasma and much more higher lipophilicity than that of the un...

The synthesis of mononucleoside and dinucleoside phosphates and H-phosphonates bearing boron cluster complexes of cobalt or iron is described. The proposed method provides key synthons for the preparation of bioinorganic DNA/metallacarborane conjugates for a variety of applications.

Metallacarboranes as electrochemical labels are proposed. The electrochemical properties of nucleoside conjugates, derivatives of thymidine (T), 2′-deoxycytidine (dC), 2′-deoxyadenosine (dA) and 2′-deoxyguanosine (dG), containing metallacarborane complex of cobalt or iron are described. A multielectrochemical detection using specific metallacarbora...

The structure of the title compound, C6H13NO4S·H2O or OC4H8NHCH2CH2SO3·H2O, was redetermined at 100 (1) K using synchrotron radiation. The water mol-ecule, in contrast to the results of the prior roomerature study [Christensen, Haxell, Lehmann & Nielsen (1993). Acta Chem. Scand. 47, 753-756], was found to be disordered over two positions. The disor...

The structure of the title compound, C6H13NO4S·H2O or OC4H8NHCH2CH2SO3·H2O, was redetermined at 100 (1) K using synchrotron radiation. The water mol­ecule, in contrast to the results of the prior room-temperature study [Christensen, Haxell, Lehmann & Nielsen (1993). Acta Chem. Scand.47, 753–756], was found to be disordered over two positions. The d...

Modification of 2'-deoxyadenosine at position 8 with para-carborane boron cluster is described. Incorporation of boron cluster into nucleic base has been accomplished using Sonogashira palladium-catalyzed cross-coupling reaction or, alternatively, Huisgen "click" type reaction. These are the first examples of adenosine derivatives with hydrophobic...

A general approach to the synthesis of nucleoside conjugates between derivatives of thymidine (T), 2'-O-deoxycytidine (dC), 2'-O-deoxyadenosine (dA), and 2'-O-deoxyguanosine (dG), and metallacarborane complexes is described. Metallacarborane-nucleoside derivatives are prepared by reaction of the dioxane-metallacarborane adduct with a base-activated...

Borane clusters as potential infrared label for nucleic acids are proposed. The unique infrared absorption of BH bond of the boranes is located in the window of nucleic acids transparency (2400–2650 cm−1). Fourier transform infrared spectroscopy characteristics of several carborane (–C2B10H11) and metallacarborane [3-Co-(1,2-C2B9H11)]− containing n...

Thymidine conjugates containing metallacarborane, {8-[5-(N(3)-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}- (5) and {8-[5-(O(4)-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}- (6) ions and several simple [3-cobalt bis(1,2-dicarbollide)]- ion (1) derivatives have been studied as potential boron carriers for BNCT. Compound 6 a...

The carboranyl cage is a new modifying entity for nucleosides, DNA oligonucleotides, and other biomolecules. Herein, the first reliable method for the synthesis of nucleosides modified with a carborane cluster at the 2′-position is described.

Contemporary technologies take advantage of the knowledge of different fields of science. The crossroads of biology and material engineering and further, biological and inorganic chemistry is a field of most fruitful interconnections, yielding new pharmaceuticals, diagnostic methods, new materials such as biological/nonbiological composites, and ne...

Nucleosid-Metallacarboran-Konjugate (z. B. TBEMC; siehe Bild) mit niedriger Toxizität wurden synthetisiert und als Redoxmarker mit DNA-Oligonucleotiden verknüpft. Die markierten Oligonucleotide wirken als Primer für die Taq-Polymerase.

The carboranyl cage is a new modifying entity for nucleosides and DNA-oligonucleotides. Most of carborane–nucleoside conjugates described so far belong to pyrimidine series. Herein, the first synthesis of adenosine, nucleoside containing purine nucleic base, modified with carborane cluster, is described.

Human cytomegalovirus (HCMV) infects about 60% of adults in developed world and more than 90% of developing countries population. In the immunocompetent host, initial infection and reactivation of latent infection are usually asymptomatic. However, in hosts with impaired cellular immune functions, such as transplant recipients, patients infected wi...

Boronated oligonucleotides are potential candidates for boron neutron capture therapy (BNCT), antisense oligonucleotide technology (AOT), and as tools in molecular biology. The resistance of oligonucleotides against nucleolytic enzymes is an essential property for their pharmacological applications. To evaluate the stability of novel DNA-oligomers...

Boronated oligonucleotides are potential candidates for antisense oligonucleotide technology (AOT), boron neutron capture therapy (BNCT), and as tools in molecular biology. A method was developed for the solid phase synthesis of oligonucleotides containing 2'-O-(o-carboran-1-yl-methyl) (2'-CBM) group. Synthesis was performed using a standard beta-c...

Fast and simple methodology for the assignment of the absolute configuration at the phosphorus atom in diastereomerically pure Rp and Sp 5'-O-monomethoxytrityl-2'-O-deoxynucleoside 3'-O-(O-4-nitrophenyl) methanephosphonate (3) was established. The method utilizes 2D ROESY NMR and can be used for the stereochemical analysis of other P-chiral mononuc...

DNA chip technology is rapidly advancing and applications to diagnostics (mutation detection), gene discovery, gene expression and mapping have been convincingly demonstrated. Array-based assays allow a range of characteristics, such as drug resistance, to be rapidly and simultaneously determined. Near instantaneous detection of pathogens from clin...

Boronated oligonucleotides are potential candidates for antisense oligonucleotide technology (AOT), boron neutron capture therapy (BNCT), and as tools in molecular biology. A method was developed for the solid phase synthesis of oligonucleotides containing 2'-0-(o-carboran-1-yl-methyl) (2'-CBM) group. Synthesis was performed using a standard beta-c...