U organskoj kemiji sve se više pažnje posvećuje sintezi u mikro- i mezo- protočnim sustavima (engl. flow chemistry), koja ima brojne prednosti nad šaržnom sintezom. Glavne prednosti provedbe organske ...sinteze u takvim protočnim reaktorima su veća učinkovitost, ekološka prihvatljivost i sigurnost. Unatoč tome sinteza u protočnim sustavima ne može se primjenjivati kao univerzalni pristup za sve probleme koji mogu zateći organske sintetske kemičare te prije provedbe odabranih reakcija treba razmotriti isplativost s obzirom na šaržnu sintezu. Sigurnosti i ekološkoj prihvatljivosti sinteza u protočnim reaktorima značajno doprinosi upotreba malog volumena kemikalija i otapala budući da se reakcije provode u mikro- ili mezo- reaktorima napravljenima u pravilu od inertnih materijala. Zbog brojnih prednosti, organske reakcije u protočnim sustavima predmet su kontinuiranog istraživanja, pri čemu se uvjeti provedbe reakcija optimiraju u svrhu povećanja učinkovitosti i sigurnosti procesa te njegova uvećanja.
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The identification of novel molecular systems with high fluorescence and significant non-linear optical (NLO) properties is a hot topic in the continuous search for new emissive probes. Here, the ...photobehavior of three two-arm bis(dimethylamino)styrylbenzene derivatives, where the central benzene was replaced by pyridine, furan, or thiophene, was studied by stationary and time-resolved spectroscopic techniques with ns and fs resolution. The three molecules under investigation all showed positive fluorosolvatochromism, due to intramolecular charge-transfer (ICT) dynamics from the electron-donor dimethylamino groups, and significant fluorescence quantum yields, because of the population of a planar and emissive ICT state stabilized by intramolecular hydrogen-bond-like interactions. The NLO properties (hyperpolarizability coefficient and TPA cross-section) were also measured. The obtained results allowed the role of the central heteroaromatic ring to be disclosed. In particular, the introduction of the thiophene ring guarantees high fluorescent quantum yields irrespective of the polarity of the medium, and the largest hyperpolarizability coefficient because of the increased conjugation. An important and structure-dependent involvement of the triplet state was also highlighted, with the intersystem crossing being competitive with fluorescence, especially in the thiophene derivative, where the triplet was found to significantly sensitize molecular oxygen even in polar environment, leading to possible applications in photodynamic therapy.
Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative ...disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles
-
, as well as 1,2,3-triazolium salts
-
were synthesized and tested. Triazolium salts
-
showed excellent activity while salts
and
showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules
-
. The representative of newly prepared compounds,
and
, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases' active sites identified cation-π interactions as the most responsible for the stability of the enzyme-ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed.
A new series of 4
-1,3-benzothiazine dyes were prepared and fully characterized in an aqueous medium. Benzothiazine salts were synthesized either through the classical synthetic pathway using ...Buchwald-Hartwig amination or through economical and environmentally friendly electrochemical synthesis. The latest synthetic approach employs successful electrochemical intramolecular dehydrogenative cyclization of
-benzylbenzenecarbothioamides to form 4
-1,3-benzothiazines. 4
-1,3-Benzothiazines were evaluated as novel DNA/RNA probes. Through the use of several methods such as UV/vis spectrophotometric titrations, circular dichroism and thermal melting experiments, the binding of four benzothiazine-based molecules to polynucleotides was examined. Compounds
and
acted as DNA/RNA groove binders, thus suggesting the potential of these compounds as novel DNA/RNA probes. This is a proof-of-concept study and will be expanded to include SAR/QSAR studies.
This study aims to test the inhibition potency of new thienobenzo/naphtho-triazoles toward cholinesterases, evaluate their inhibition selectivity, and interpret the obtained results by molecular ...modeling. The synthesis of 19 new thienobenzo/naphtho-triazoles by two different approaches resulted in a large group of molecules with different functionalities in the structure. As predicted, most prepared molecules show better inhibition of the enzyme butyrylcholinesterase (BChE), considering that the new molecules were designed according to the previous results. Interestingly, the binding affinity of BChE for even seven new compounds (
,
,
,
,
,
, and
) was similar to that reported for common cholinesterase inhibitors. According to computational study, the active thienobenzo- and naphtho-triazoles are accommodated by cholinesterases through H-bonds involving one of the triazole's nitrogens, π-π stacking between the aromatic moieties of the ligand and aromatic residues of the active sites of cholinesterases, as well as π-alkyl interactions. For the future design of cholinesterase inhibitors and search for therapeutics for neurological disorders, compounds with a thienobenzo/naphtho-triazole skeleton should be considered.
Psychological problems of patients with cancer Gregurek, Rudolf; Bras, Marijana; Dordević, Veljko ...
Psychiatria Danubina,
06/2010, Letnik:
22, Številka:
2
Journal Article, Conference Proceeding
Odprti dostop
Psycho-oncology is a broad approach to cancer therapy which treats the emotional, social, and spiritual distress which often accompanies cancer patients. The development of psycho-oncology began in ...the second part of the 20th century reflecting the increased interest in the study of cancer patients' psychological reactions to their illness at all stages of its course, and the analysis of the emotional, spiritual, social, and behavioral factors which influence the risk of developing cancer and long-term aftercare treatment. Today the psycho-oncology has become an accepted part of cancer treatment, with departments of psycho-oncology established in most major cancer centers in Canada, the United States and many Western European countries. A key clinical challenge for the oncologist is differentiating the expected and transient distress associated with cancer from the excessive, disabling distress requiring psychiatric interventions. One third of patients with cancer will experience distress which requires evaluation and treatment, and the most common psychiatric disorders are depression, anxiety disorders and adjustment disorders. Psychiatrists should be involved in the multidisciplinary treatment team who work with the cancer patients. Further research is needed to determine the effectiveness of different psychological and psychopharmacological interventions in psycho-oncology and palliative medicine. Mental health issues should be included in the training of health care professionals in all areas of medicine, psychology and social work to meet the demands of cancer patients.
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•Photochemical and photophysical characteristics of novel triazolo-stilbenes.•Unreactivity in intramolecular photocycloadditions and electrocyclizations.•DFT approach for explaining ...configuration and substituent effects.
The synthesis, photoreactivity, and spectroscopic characterization of novel 1,2,3-triazole di-heterostilbenes bearing various aliphatic and aromatic substituents on the triazole rings were thoroughly explored. By introducing triazole rings into the o-divinylbenzene moiety, compared with the 2-furyl and 2-thienyl heteroanalogues, these compounds did not show any photochemical reactivity toward intramolecular cycloaddition reactions or electrocyclization processes. The research is further extended to the more in-depth examination of photochemical and photophysical characteristics of the investigated triazolo-stilbenes to explain the lack of reactivity in intramolecular photochemical cyclizations by configuration and substituent effects. Conformations of synthetically obtained novel triazoles are examined by Density Functional Theory (DFT). The time dependent-DFT approach was employed to obtain additional insight into the properties observed with UV/Vis spectroscopy. The frontier orbital energy was computationally investigated to determine the influence of cis–trans isomerism and the nature of substituents on the spectroscopic properties of the triazoles. Along with our previous studies of similar compounds containing furan and thiophene, respectively, this study shows that introducing various heteroaromatic rings induces diverse photochemistry and photophysics due to the conformational changes and change in electronic distribution within the molecular system.
1,2,3-Triazole-4-carbaldehydes are useful synthetic intermediates which may play an important role in the discovery of novel applications of the 1,2,3-triazole moiety. In this work, a one-step ...multigram scale synthesis of 4-formyl-1-(4-nitrophenyl)-1H-1,2,3-triazole (FNPT) as a preferred reagent for the synthesis of 1-alkyl-4-formyltriazoles is described, making use of the commercially available 3-dimethylaminoacrolein and 4-nitrophenyl azide. Next, the earlier reported reaction of FNPT with alkylamines is further explored, and for hexylamine, the one-pot sequential cycloaddition and Cornforth rearrangement is demonstrated. In addition, a useful protocol for the in situ diazotization of 4-nitroaniline is provided. This facilitated the complete hydrolysis of rearranged 4-iminomethyl-1,2,3-triazoles and allowed for the recycling of 4-nitrophenyl azide.
The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the ...peripheral and central nervous systems (CNS) leading to cholinergic crisis. The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. Oximes in use have quaternary nitrogens, and therefore poorly cross the brain–blood barrier. In this work, we synthesized novel uncharged thienostilbene oximes by the Wittig reaction, converted to aldehydes by Vilsmeier formylation, and transformed to the corresponding uncharged oximes in very high yields. Eight trans,anti- and trans,syn-isomers of oximes were tested as reactivators of nerve-agent-inhibited AChE and BChE. Four derivatives reactivated cyclosarin-inhibited BChE up to 70% in two hours of reactivation, and docking studies confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on the moderate binding affinity of both AChE and BChE for all selected oximes, and in silico evaluated ADME properties regarding lipophilicity and CNS activity, these compounds present a new class of oximes with the potential for further development of CNS-active therapeutics in OP poisoning.
Promising test results on biological activity of our previously described benzobicyclo3.2.1octadienes, synthetically obtained by intramolecular photochemical cycloaddition reaction, prompted us to ...pursue with the further functionalization of this basic skeleton toward oxime derivatives. The free energies of formation of complexes between planned new oximes showing promising ADME properties and the active sites of cholinesterases were calculated using docking and density functional theory, showing that thermodynamical stability of some of the examined complexes is the same as the stability of the complex formed with well known and efficient cholinesterase inhibitor huperzine A. On the basis of calculated stabilities of complexes, the synthesis of several representative new compounds was succesfully performed. In some cases, the furan ring opened on two different ways so different opened oximes and oxime ethers were also formed. All new prepared oximes and oxime ethers present good material for further experimental investigation as inhibitors/reactivators of cholinesterases.
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•The stabilities of complexes between oximes and cholinesterases were calculated by DFT.•On the basis of calculations synthesis of new compounds was performed.•Oximes and oxime ethers will be explored as potential inhibitors of cholinesterases.
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