• Publikační typ
• abstrakt z konference MeSH

Salicylanilides have proved their activity against tuberculosis (TB). One weak electron-withdrawing substituent is favored at the salicylic part, specially Cl or Br atoms at positions 4 or 5. On the other hand, the antimycobacterial activity of salicylanilides is negatively affected when a strong electron-withdrawing substituent (NO2) is present at the same positions. Herein we describe the synthesis and characterization of novel salicylanilides possessing two weak electron-withdrawing groups (halogen atoms) at their salicylic part and compare their antitubercular activity with their monohalogenated analogues. All dihalogenated derivatives proved to possess antitubercular activity at a very narrow micromolar range (MIC=1-4μM), similar with their most active monohalogenated analogues. More importantly, the most active final molecules were further screened against multidrug resistant strains and found to inhibit their growth at the range of 0.5-4μM.

• MeSH
• antituberkulotika chemická syntéza   chemie   farmakologie   MeSH
• buňky Hep G2 MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• multirezistentní tuberkulóza farmakoterapie   MeSH
• Mycobacterium účinky léků   růst a vývoj   MeSH
• salicylanilidy chemická syntéza   chemie   farmakologie   MeSH
• salicylany chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The oxidative photocyclization of aromatic Schiff bases was investigated as a potential method for synthesis of phenanthridine derivatives, biologically active compounds with medical applications. Although it is possible to prepare the desired phenanthridines using such an approach, the reaction has to be performed in the presence of acid and TEMPO to increase reaction rate and yield. The reaction kinetics was studied on a series of substituted imines covering the range from electron-withdrawing to electron-donating substituents. It was found that imines with electron-withdrawing substituents react one order of magnitude faster than imines bearing electron-donating groups. The 1H NMR monitoring of the reaction course showed that a significant part of the Z isomer in the reaction is transformed into E isomer which is more prone to photocyclization. The portion of the Z isomer transformed showed a linear correlation to the Hammett substituent constants. The reaction scope was expanded towards synthesis of larger aromatic systems, namely to the synthesis of strained aromatic systems, e.g., helicenes. In this respect, it was found that the scope of oxidative photocyclization of aromatic imines is limited to the formation of no more than five ortho-fused aromatic rings.

• MeSH
• cykloadiční reakce metody   MeSH
• fenantridiny chemická syntéza   MeSH
• fotochemické oxidanty chemie   MeSH
• fotochemické procesy MeSH
• oxidace-redukce MeSH
• Schiffovy báze chemie   MeSH
• Publikační typ
• časopisecké články MeSH

A method for preparation of a new stable Cu(I) catalyst supported on weakly acidic polyacrylate resin without additional stabilizing ligands is described. A simple and efficient methodology for Ullmann Cu(I) catalyzed C-N cross coupling reactions using this original catalyst is reported. Coupling reactions of 4-chloropyridinium chloride with anilines containing electron donating (EDG) or electron withdrawing (EWG) groups, naphthalen-2-amine and piperazine, respectively, are successfully demonstrated.

• MeSH
• 2-naftylamin chemie   MeSH
• akrylové pryskyřice chemie   MeSH
• aniliny chemie   MeSH
• elektrony * MeSH
• katalýza MeSH
• koncentrace vodíkových iontů MeSH
• měď chemie   MeSH
• opakované použití vybavení MeSH
• piperaziny chemie   MeSH
• pyridinové sloučeniny chemická syntéza   MeSH
• technologie zelené chemie MeSH
• Publikační typ
• časopisecké články MeSH

N-Benzyl-2-nitrobenzenesulfonamides underwent base-mediated intramolecular arylation at the benzyl sp(3) carbon to yield benzhydrylamines. The presence of electron withdrawing groups on the aromatic ring of the benzyl group was required to facilitate the C-arylation. Unsymmetrically substituted benzhydrylamines are advanced intermediates toward nitrogenous heterocycles, as exemplified in the syntheses of indazole oxides and quinazolines.

• MeSH
• alkoholy chemie   MeSH
• benzhydrylové sloučeniny chemie   MeSH
• benzylové sloučeniny chemie   MeSH
• chinazoliny chemická syntéza   MeSH
• heterocyklické sloučeniny chemická syntéza   MeSH
• indazoly chemická syntéza   MeSH
• indikátory a reagencie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid.

• MeSH
• antiinfekční látky * chemická syntéza   chemie   farmakologie   MeSH
• Candida glabrata růst a vývoj   MeSH
• chalkon * chemická syntéza   chemie   farmakologie   MeSH
• halogenované uhlovodíky * chemická syntéza   chemie   farmakologie   MeSH
• Mycobacterium růst a vývoj   MeSH
• pyraziny * chemická syntéza   chemie   farmakologie   MeSH
• Trichophyton růst a vývoj   MeSH
• Publikační typ
• časopisecké články MeSH

Photolysis of dihydroxy compounds (diols) protected as 2-nitrobenzylidene acetals (ONBA) and subsequent acid- or base-catalyzed hydrolysis of the 2-nitrosobenzoic acid ester intermediates result in an efficient and high-yielding release of the substrates. We investigated the scope and limitations of ONBA photochemistry and expanded upon earlier described two-step procedures to show that the protected diols of many structural varieties can also be liberated in a one-pot procedure. In view of the fact that the acetals of nonsymmetrically substituted diols are converted into one of the corresponding 2-nitrosobenzoic acid ester isomers with moderate to high regioselectivity, the mechanism of their formation was studied using various experimental techniques. The experimental data were found to be in agreement with DFT-based quantum chemical calculations that showed the preferential cleavage occurs on the acetal C-O bond in the vicinity of more electron-withdrawing (or less electron-donating) groups. The study also revealed considerable complexity in the cleavage mechanism and that the structural variations in the substrate can significantly alter the reaction pathway. This deprotection strategy was found to be also applicable for 2-thioethanol when released from the corresponding monothioacetal in the presence of a reducing agent, such as ascorbic acid.

• MeSH
• acetaly chemie   MeSH
• benzylidenové deriváty chemie   MeSH
• chemické modely MeSH
• fotochemie MeSH
• fotolýza MeSH
• kvantová teorie MeSH
• počítačová simulace MeSH

In this paper, we studied a designed series of aldose reductase (AR) inhibitors. The series was derived from a known AR binder, which had previously been shown to form a halogen bond between its bromine atom and the oxygen atom of the Thr-113 side chain of AR. In the series, the strength of the halogen bond was modulated by two factors, namely bromine-iodine substitution and the fluorination of the aromatic ring in several positions. The role of the single halogen bond in AR-ligand binding was elucidated by advanced binding free energy calculations involving the semiempirical quantum chemical Hamiltonian. The results were complemented with ultrahigh-resolution X-ray crystallography and IC50 measurements. All of the AR inhibitors studied were shown by X-ray crystallography to bind in an identical manner. Further, it was demonstrated that it was possible to decrease the IC50 value by about 1 order of magnitude by tuning the strength of the halogen bond by a monoatomic substitution. The calculations revealed that the protein-ligand interaction energy increased upon the substitution of iodine for bromine or upon the addition of electron-withdrawing fluorine atoms to the ring. However, the effect on the binding affinity was found to be more complex due to the change of the solvation/desolvation properties within the ligand series. The study shows that it is possible to modulate the strength of a halogen bond in a protein-ligand complex as was designed based on the previous studies of low-molecular-weight complexes.

• MeSH
• aldehydreduktasa antagonisté a inhibitory   chemie   MeSH
• halogeny chemie   MeSH
• inhibiční koncentrace 50 MeSH
• inhibitory enzymů chemie   MeSH
• krystalografie rentgenová MeSH
• molekulární modely MeSH
• počítačová simulace MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• chemie MeSH

• Konspekt
• Organická chemie
• NLK Obory
• chemie, klinická chemie
• NLK Publikační typ
• učebnice vysokých škol

In search of novel targets for influenza inhibitors, a site on PB1 was selected for its high conservation and probable interaction with a host protein, RanBP5, that is key to nuclear import of PB1, where it complexes with PB2, PA, and NP to transcribe viral RNA. Docking with libraries of drug-like compounds led to a selection of five candidates that bound tightly and with a pose likely to inhibit protein binding. These were purchased and tested in vitro, found to be active, and then one was synthetically expanded to explore the structure-activity relationship. The top candidates had a carboxylic acid converted to an ester and electron-withdrawing substituents added to a phenyl group in the original structure. Resistance was slow to develop, but cytotoxicity was moderately high. Nuclear localization of PB1 and in vitro polymerase activity were both strongly inhibited.

• MeSH
• beta karyoferiny metabolismus   MeSH
• chřipka lidská farmakoterapie   MeSH
• lidé MeSH
• objevování léků MeSH
• počítačová simulace MeSH
• replikace viru účinky léků   MeSH
• rychlé screeningové testy MeSH
• simulace molekulového dockingu MeSH
• virové proteiny antagonisté a inhibitory   MeSH
• virus chřipky A účinky léků   enzymologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH