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.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- borany chemie farmakologie MeSH
- buněčné linie MeSH
- buňky Hep G2 MeSH
- DNA nádorová účinky léků MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- molekulární struktura MeSH
- naftalimidy chemie farmakologie MeSH
- organokovové sloučeniny chemická syntéza chemie farmakologie MeSH
- oxidační stres účinky léků MeSH
- proliferace buněk účinky léků MeSH
- vazebná místa MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ring cleavage of cyclic ether substituents attached to a boron cage via an oxonium oxygen atom are amongst the most versatile methods for conjoining boron closo-cages with organic functional groups. Here we focus on much less tackled chemistry of the 11-vertex zwitterionic compound [10-(O-(CH2-CH2)2O)-nido-7,8-C2B9H11] (1), which is the only known representative of cyclic ether substitution at nido-cages, and explore the scope for the use of this zwitterion 1 in reactions with various types of nucleophiles including bifunctional ones. Most of the nitrogen, oxygen, halogen, and sulphur nucleophiles studied react via nucleophilic substitution at the C1 atom of the dioxane ring, followed by its cleavage that produces six atom chain between the cage and the respective organic moiety. We also report the differences in reactivity of this nido-cage system with the simplest oxygen nucleophile, i.e., OH-. With compound 1, reaction proceeds in two possible directions, either via typical ring cleavage, or by replacement of the whole dioxane ring with -OH at higher temperatures. Furthermore, an easy deprotonation of the hydrogen bridge in 1 was observed that proceeds even in diluted aqueous KOH. We believe this knowledge can be further applied in the design of functional molecules, materials, and drugs.
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.
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1-) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.
- MeSH
- amidy chemie MeSH
- biologický transport účinky léků MeSH
- borany chemie farmakologie MeSH
- doxorubicin metabolismus MeSH
- inhibitory karboanhydras chemie farmakologie MeSH
- karboanhydrasa IX chemie metabolismus MeSH
- katalytická doména MeSH
- lidé MeSH
- molekulární modely MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- racionální návrh léčiv MeSH
- synergismus léků MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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
- borany chemie MeSH
- chalkogeny chemie MeSH
- krystalizace MeSH
- molekulární modely MeSH
- statická elektřina MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
An aminoborane side product from the nicergoline manufacture process was identified by single-crystal X-ray diffraction. As boranes of pharmaceutical molecules are quite rare, the binding potential of the BH3 group was investigated and compared with similar compounds using Cambridge Structural Database (CSD). Surprisingly, the packing was stabilized by a dihydrogen bond, which triggered a false alert for too-short contact of hydrogen atoms in IUCR checkCIF. As the dihydrogen bond concept is not widely known, such an alert might mislead crystallographers to force -CH3 optimal geometry to -BH3 groups. The B-H distances equal to or less than 1.0 Å (17% of the CSD structures) are substantially biased when analyzing the structures of aminoborane complexes in CSD. To conduct proper searching, B-H bond length normalization should be applied in the CSD search.
BF3·Et2O-catalyzed double aldol condensation between acetylated steroid sapogenins and terephtalaldehyde led to acetylated dimeric spirostanols linked through a 1,4-dimethylidenebenzene moiety in moderate to good yields. The E configurations of the introduced double bonds were corroborated by NOE experiments. Saponification of the dimeric steroids led to the corresponding dimeric spirostanols.
- MeSH
- aldehydy chemie MeSH
- benzen chemie MeSH
- borany chemie MeSH
- dimerizace * MeSH
- ether chemie MeSH
- katalýza MeSH
- kyseliny ftalové chemie MeSH
- sapogeniny chemie MeSH
- spirostany chemická syntéza chemie MeSH
- stereoizomerie MeSH
- techniky syntetické chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study, selective green synthesis of gold nanoparticles (nAu) with the use of Tarragon extract (Artemisia dracunculus) was investigated. Characterization of the synthetized nAu was carried out using several techniques including: UV-Vis, SEM, zeta potential analysis, DLS, and ATR-FTIR. Based on measurements of Tarragon extract by HPLC-MS, significant chemical substances participating as reducing and stabilizing agents were identified. FTIR confirmed typical functional groups that could be found in these acids on the nAu surface, such as O-H, C=O and C-O. The effects of various parameters (concentration of Tarragon extract, Au precursor, and initial pH of the synthesis) on the shape and size of the nanoparticles have been investigated. UV-Vis and SEM confirmed the formation of nAu at various concentrations of the extract and Au precursor and showed correlation between the added extract concentration and shift in maximal absorbance towards higher frequencies, indicating the formation of smaller nanoplates. Zeta potential determined at various pH levels revealed that its value decreased with pH, but for all experiments in the pH range of 2.8 to 5.0, the value is below - 30 mV, an absolute value high enough for long-term nAu stability. In order to evaluate nAu catalytic activity, the reduction of 4-nitrophenol to 4-aminophenol by sodium borohydride was used as a model system. The reaction takes place 1.5 times faster on Au-triangles than on Au-spherical NPs.
- MeSH
- aminofenoly chemie MeSH
- borohydridy chemie MeSH
- katalýza MeSH
- koncentrace vodíkových iontů MeSH
- kovové nanočástice chemie MeSH
- mikroskopie elektronová rastrovací MeSH
- nitrofenoly chemie MeSH
- pelyněk chemie MeSH
- rostlinné extrakty analýza chemie MeSH
- spektrofotometrie ultrafialová MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- tandemová hmotnostní spektrometrie MeSH
- technologie zelené chemie metody MeSH
- velikost částic MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zlato chemie MeSH
- Publikační typ
- časopisecké články MeSH
Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.
- MeSH
- alfa částice terapeutické užití MeSH
- bor chemie terapeutické užití MeSH
- borohydridy chemie MeSH
- buněčná smrt účinky záření MeSH
- chromozomální aberace účinky záření MeSH
- cyklotrony MeSH
- DNA nádorová genetika metabolismus účinky záření MeSH
- fluorescenční barviva chemie MeSH
- izotopy uhlíku chemie MeSH
- karyotypizace MeSH
- kombinovaná terapie přístrojové vybavení metody MeSH
- lidé MeSH
- lineární přenos energie MeSH
- nádorové buněčné linie MeSH
- nádory prostaty patologie radioterapie MeSH
- neutrony * MeSH
- poškození DNA MeSH
- protonová terapie * přístrojové vybavení metody MeSH
- relativní biologická účinnost MeSH
- sulfhydrylové sloučeniny chemie MeSH
- terapie metodou neutronového záchytu (bor-10) přístrojové vybavení metody MeSH
- vztah dávky záření a odpovědi MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
