- Syntheses and crystal structures of Ni(II) complexes with pyridine-based macrocyclic ligands
-
Three pyridine-based macrocyclic ligands, two containing one pyridine pendant arm (L1 and L2) and one containing piperazine rings in the macrocyclic scaffold (L3), with an increasing size of the macrocycle from 12-, 14- to 30-membered ring for L1–L3 were synthesized and characterized. A series of Ni(II) complexes with all these ligands, with molecular formulas [NiL1(CH3OH)](ClO4)2 (1), [NiL2(CH3CN)](ClO4)2 (2), and [Ni2L3(DMF)2(CH3CN)2](ClO4)4 (3) (DMF = N,N–dimethylformamide), was prepared and thoroughly characterized. Single crystal X-ray structural analysis confirmed that all the complexes have a coordination number of six and their geometries are close to octahedral. In the case of the mononuclear complexes 1 and 2, all the nitrogen atoms of the macrocycle are coordinated, however, in the dinuclear complex 3 with the piperazine-based ligand L3, two nitrogen donor atoms (of the total number of ten) are uncoordinated. The first coordination spheres of all the complexes are completed by solvent molecules. The values of effective magnetic moments, determined by the Evans method in solution, are 3.12, 3.19 and 4.36 μB for complexes 1, 2 and 3, respectively, which correspond well to the theoretical spin-only values.
- Císa?ová, Ivana,Draho?, Bohuslav,Zahradníková, Eva
-
supporting information
(2021/11/17)
-
- CENTRALLY ACTIVE AND ORALLY BIOAVAILABLE UNCHARGED BISOXIME ANTIDOTES FOR ORGANOPHOSPHATE POISONING AND METHODS FOR MAKING AND USING THEM
-
In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.
- -
-
Page/Page column 38; 41-42
(2020/12/07)
-
- DNA sequence-specific ligands: XVI. Series of the DBP(n) fluorescent dimeric bisbenzimidazoles with 1,4-piperazine-containing linkers
-
A novel series of the DBP(n) fluorescent symmetric dimeric bisbenzimidazoles in which the bisbenzimidazole fragments were attached to an oligomeric linker with the 1,4-piperazine residue in its center were prepared. The DBP(n) molecules were distinguished by the number of methylene groups n (where n = 1, 2, 3, 4) in the linker. The DBP(n) synthesis was based on a condensation of the monomeric bisbenzimidazole (MB) with 1,4-piperazinedialkylcarbonic acids. The ability of the DBP(n) dimeric bisbenzimidazoles to form complexes with the double-stranded DNA was demonstrated by a complex of physicochemical methods, including spectroscopy in the visual UV-area, circular dichroism (CD), and fluorescence. The DBP(1–4) molecules were localized in the DNA minor groove by the CD method with the use of cholesteric liquid-crystalline dispersions (CLCD) of the double-stranded DNA. The DBP(n) dimeric bisbenzimidazoles were easily soluble in water, penetrated through cellular and nuclear membranes, and stained DNA in living cells distinct from the previously synthesized DB(n) series.
- Koval,Ivanov,Salyanov,Stomakhin,Oleinikov,Zhuze
-
p. 143 - 149
(2017/04/24)
-
- DNA specific fluorescent symmetric dimeric bisbenzimidazoles DBP(n): The synthesis, spectral properties, and biological activity
-
A series of new fluorescent symmetric dimeric bisbenzimidazoles DBP(n) bearing bisbenzimidazole fragments joined by oligomethylene linkers with a central 1,4-piperazine residue were synthesized. The complex formation of DBP(n) in the DNA minor groove was demonstrated. The DBP(n) at micromolar concentrations inhibit in vitro eukaryotic DNA topoisomerase I and prokaryotic DNA methyltransferase (MTase) M.SssI. The DBP(n) were soluble well in aqueous solutions and could penetrate cell and nuclear membranes and stain DNA in live cells. The DBP(n) displayed a moderate effect on the reactivation of gene expression.
- Ivanov, Alexander A.,Koval, Vasiliy S.,Susova, Olga Yu.,Salyanov, Victor I.,Oleinikov, Vladimir A.,Stomakhin, Andrey A.,Shalginskikh, Natalya A.,Kvasha, Margarita A.,Kirsanova, Olga V.,Gromova, Elizaveta S.,Zhuze, Alexei L.
-
supporting information
p. 2634 - 2638
(2015/06/08)
-
- COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
-
The present disclosure is directed to corn- pounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/ or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract
- -
-
Page/Page column 219
(2010/08/04)
-
- Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors
-
A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N,N′-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin- 2-yl)]propane-2-ethanediamine (9) and the N,N′-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin- 2-yl)]butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours π-π stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 μM concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation.
- Filosa, Rosanna,Peduto, Antonella,Di Micco, Simone,Caprariis, Paolo de,Festa, Michela,Petrella, Antonello,Capranico, Giovanni,Bifulco, Giuseppe
-
experimental part
p. 13 - 24
(2011/02/25)
-
- Cyanomethylamines and azidomethylamines: new general methods of the synthesis and transformations
-
Simple and efficient methods have been developed to obtain cyanomethylamines and azidomethylamines using reactions of methoxymethylamines with TMSCN and TMSN3, respectively. In the case of dimethylformamide dimethylacetal, only one MeO group wa
- Nabiev, Orudzh G.,Nabizade, Zargalam O.,Kostyanovsky, Remir G.
-
experimental part
p. 281 - 283
(2010/01/18)
-
- Novel combi-molecules having EGFR and DNA targeting properties
-
A series of new chemical agents that demonstrate anti-tumor activity are described. The new chemical agents combine two major mechanisms of anti-tumor action. In an embodiment, the agents are capable of both inhibiting EGFR and damaging DNA while also, upon degradation, degrading to an inhibitor of EGFR and to an agent capable of damaging DNA. Moreover, a novel series of molecules capable of releasing two moles of EGFR inhibitor and a potent bi-functional alkylating agent are also described.
- -
-
Page/Page column 14; 24
(2010/02/15)
-
- Bisintercalating Threading Diacridines: Relationships between DNA Binding, Cytotoxicity, and Cell Cycle Arrest
-
We have synthesized a series of bis(9-aminoacridine-4-carboxamides) linked via the 9-position with neutral flexible alkyl chains, charged flexible polyamine chains, and a semirigid charged piperazine-containing chain. The carboxamide side chains comprise N,N-dimethylaminoethyl and ethylmorpholino groups. The compounds are designed to bisintercalate into DNA by a threading mode, in which the side chains are intended to form hydrogen-bonding contacts with the O6/N7 atoms of guanine in the major groove, and the linkers are intended to lie in the minor groove. By this means, we anticipate that they will dissociate slowly from DNA, and be cytotoxic as a consequence of template inhibition of transcription. The dimers remove and reverse the supercoiling of closed circular DNA with helix unwinding angles ranging from 26° to 46°, confirming bifunctional intercalation in all cases, and the DNA complexes of representative members dissociate many orders of magnitude more slowly than simple aminoacridines. Cytotoxicity for human leukemic CCRF-CEM cells was determined, the most active agents having IC50 values of 35-50 nM in a range extending over 20-fold, with neither the dimethylaminoethyl nor the ethylmorpholino series being intrinsically more toxic. In common with established transcription inhibitors, the morpholino series, with one exception, have no effect on cell cycle distribution in randomly dividing CCRF-CEM populations. By contrast, the dimethylaminoethyl series, with two exceptions, cause G2/M arrest in the manner of topoisomerase poisons, consistent with possible involvement of topoisomerases in their mode of action. Thus, the cellular response to these bisintercalating threading agents is complex and appears to be determined by both their side chain and linker structures. There are no simple relationships between structure, cytotoxicity, and cell cycle arrest, and the origins of this complexity are unclear given that the compounds bind to DNA by a common mechanism.
- Wakelin, Laurence P. G.,Bu, Xianyong,Eleftheriou, Alexandra,Parmar, Alpesh,Hayek, Charbel,Stewart, Bernard W.
-
p. 5790 - 5802
(2007/10/03)
-
- INNER-SPHERE FORMATION OF N-(2-CYANOETHYL)-2-CHLOROETHYLAMINE IN THE REACTION OF TETRAKIS(2-CHLOROETHYLAMINE)DICHLORONICKEL(II) WITH ACRYLONITRILE
-
Being coordinated to Ni(II), 2-chloroethylamine reacts with acrylonitrile to form N-(2-cyanoethyl)-2-chloroethylamine.
- Ukraintsev, V. B.,Krasnov, B. A.
-
p. 1371 - 1372
(2007/10/02)
-