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- Research Support as Topic MeSH
- Publication type
- Abstracts MeSH
n background electrolyte (BGE) with the optimal methanol concentration of 30% (v/v), the ion with -NCS group bonded to a cluster boron atom exhibits the strongest interaction with alpha-cyclodextrin and the highest separation selectivity. Interaction of ions with alkyl or thioalkyl group weakens with the increasing substituent size. The ion with phenyl group exhibits the weakest interaction. Bonding of a group to boron atom weakens the ion interaction with alpha-cyclodextrin. Second substituent further weakens the interaction with alpha-cyclodextrin. Separation efficiency is lower at the presence of alpha-cyclodextrin than at its absence. This separation efficiency loss, amounts up to 90%.
Surface of ultra-high-molecular-weight polyethylene (UHMWPE) was modified by chemical methods. Surface was firstly activated by Piranha solution and then grafted with selected amino-compounds (cysteamine, ethylenediamine or chitosan). The next step was grafting of some borane cluster compounds, highly fluorescent borane hydride cluster anti-B18H22 or its thiolated derivative 4,4'-(HS)2-anti-B18H20. Polymer foils were studied using various methods to characterize surface chemistry (X-ray photoelectron spectroscopy), roughness and morphology (atomic force microscopy, scanning electron microscopy), chemistry and polarity (electrokinetic analysis), wettability (goniometry) and photophysical properties (UV-Vis spectroscopy) before and after modification steps. Subsequently some kinds of antimicrobial tests were performed. Immobilization of anti-B18H22 in small quantities onto UHMWPE surface leads to materials with a luminescence. Samples grafted with borane clusters showed significant inhibition of growth for gram-positive bacteria (S. epidermidis). These approaches can be used for (i) luminophores on the base of polymers nanocomposites development and/or (ii) preparation of materials with antimicrobial effects.
Chalcogen atoms are a class of substituents capable of generating inner and outer derivatives of boron clusters. It is well known that chalcogenated boron clusters can form strong σ-hole interactions when a chalcogen atom is a part of an icosahedron. This paper studies σ-hole interactions of dicarbaboranes with two exopolyhedral chalcogen atoms bonded to carbon vertices. Specifically, a computational investigation has been carried out on the co-crystal of (1,2-C2B10H10)2Se4•toluene and a single crystal of (1,2-C2B10H10)2Te4.
- MeSH
- Boranes chemistry MeSH
- Chalcogens chemistry MeSH
- Crystallization MeSH
- Models, Molecular MeSH
- Static Electricity MeSH
- Thermodynamics MeSH
- Publication type
- Journal Article MeSH
HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorganic compounds, icosahedral metallacarboranes, as candidates for a novel class of nonpeptidic PIs. Here, we report the potent, specific, and selective competitive inhibition of HIV PR by substituted metallacarboranes. The most active compound, sodium hydrogen butylimino bis-8,8-[5-(3-oxa-pentoxy)-3-cobalt bis(1,2-dicarbollide)]di-ate, exhibited a K(i) value of 2.2 nM and a submicromolar EC(50) in antiviral tests, showed no toxicity in tissue culture, weakly inhibited human cathepsin D and pepsin, and was inactive against trypsin, papain, and amylase. The structure of the parent cobalt bis(1,2-dicarbollide) in complex with HIV PR was determined at 2.15 A resolution by protein crystallography and represents the first carborane-protein complex structure determined. It shows the following mode of PR inhibition: two molecules of the parent compound bind to the hydrophobic pockets in the flap-proximal region of the S3 and S3' subsites of PR. We suggest, therefore, that these compounds block flap closure in addition to filling the corresponding binding pockets as conventional PIs. This type of binding and inhibition, chemical and biological stability, low toxicity, and the possibility to introduce various modifications make boron clusters attractive pharmacophores for potent and specific enzyme inhibition.
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- Aspartic Acid Endopeptidases chemistry MeSH
- Boranes pharmacology chemical synthesis chemistry MeSH
- Financing, Organized MeSH
- HIV Protease chemistry MeSH
- HIV Protease Inhibitors pharmacology chemical synthesis chemistry MeSH
- Crystallography, X-Ray MeSH
- Quantitative Structure-Activity Relationship MeSH
- Drug Design MeSH
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 several naphthalimide-carborane and metallacarborane conjugates were synthesized in the present study. Their effect on a cancer cell line - cytotoxicity, type of cell death, cell cycle, and ROS production were investigated. The tested conjugates revealed different activities than the leading members of the naphthalimides family, namely mitonafide and pinafide. These derivatives could induce G0/G1 arrest and promote mainly apoptosis in HepG2 cell line. Our investigations demonstrated that the most promising molecule is N-{[2-(3,3'-commo-bis(1,2-dicarba-3-cobalta(III)-closo-dodecaborate-1-yl)ethyl]-1'-aminoethyl)}-1,8-naphthalimide] (17). It was shown that 17 exhibited cytotoxicity against HepG2 cells, activated cell apoptosis, and caused cell cycle arrest in HepG2 cells. Further investigations in HepG2 cells revealed that compound 17 can also induce ROS generation, particularly mitochondrial ROS (mtROS), which was also proved by increased 8-oxo-dG level in DNA. Additionally to biological assays the interaction of the new compounds with ct-DNA was studied by CD spectra and melting temperature, thus demonstrating that these compounds were rather weak classical DNA intercalators.
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- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Boranes chemistry pharmacology MeSH
- Cell Line MeSH
- Hep G2 Cells MeSH
- DNA, Neoplasm drug effects MeSH
- Drug Screening Assays, Antitumor MeSH
- Humans MeSH
- Molecular Structure MeSH
- Naphthalimides chemistry pharmacology MeSH
- Organometallic Compounds chemical synthesis chemistry pharmacology MeSH
- Oxidative Stress drug effects MeSH
- Cell Proliferation drug effects MeSH
- Binding Sites MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
