Browsing by Subject "DERIVATIVES"

Sort by: Order: Results:

Now showing items 1-20 of 65
  • Aly, Ashraf A.; Hassan, Alaa A.; Bräse, Stefan; Ibrahim, Mahmoud A. A.; Abd Al-Latif, El-Shimaa S. M.; Spuling, Eduard; Nieger, Martin (2017)
    Bisthioureas reacted with either 2-(bis(methylthio)methylene)malononitrile or ethyl 2-cyano-3,3-bis(methylthio)acrylate to give 1,3,4-thiadiazoles and 1,3-thiazoles. Only, the reactive allyl derivative of bisthioureas reacted with the bis(methylthio)methylene compounds to give 1,3-thiazoles. The mechanism was discussed. The structures of products were proved by MS, IR, NMR and elemental analyses and X-ray structure analysis. [GRAPHICS]
  • Hassan, Alaa A.; Mohamed, Nasr K.; El-Shaieb, Kamal M. A.; Tawfeek, Hendawy N.; Bräse, Stefan; Nieger, Martin (2019)
    2-Substituted hydrazinecarbothioamides and N ,2-disubstituted hydrazinecarbothioamides react in high yield with dimethyl acetylenedicarboxylate (DMAD) to give 4-oxo-Z-(thiazolidin-5-ylidene) acetate derivatives. Several mechanistic options involving interaction are presented. The structures of thiazolidin-4-ones have been unambiguously confirmed by single crystal X-ray crystallography. (C) 2014 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.
  • Stepanova, Elena V.; Nagornaya, Marina O.; Filimonov, Victor D.; Valiev, Rashid R.; Belyanin, Maxim L.; Drozdova, Anna K.; Cherepanov, Victor N. (2018)
    Abstract In the present work we report that acetyl groups of per – acetylated aryl glycosides have different reactivity during the acidic deacetylation using HCl/EtOH in CHCl3, which leads to preferential deacetylation at O-3, O-4 and O-6. Thereby, the one-step preparation of 2-O-acetyl aryl glycosides with simple aglycon was accomplished for the first time. It was proved that the found reagent is to be general and unique for the preparation of series of 2-О-acetyl aryl glycosides. We have determined the influence of both carbohydrate moiety and the aglycon on the selectivity of deacetylation reaction by kinetic experiments. Using DFT/B3LYP/6-31G(d,p) and semi-empirical АМ1 methods we have found that the highest activation barrier is for 2-О-acetyl group. This completely explains the least reactivity of 2-О-acetyl group.
  • Ardashov, Oleg V.; Pavlova, Alla V.; Mahato, Arun Kumar; Sidorova, Yulia; Morozova, Ekaterina A.; Korchagina, Dina V.; Salnikov, Georgi E.; Genaev, Alexander M.; Patrusheva, Oksana S.; Li-Zhulanov, Nikolay S.; Tolstikova, Tat'yana G.; Volcho, Konstantin P.; Salakhutdinov, Nariman. F. (2019)
    We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to penetrate the blood-brain barrier (BBB). According to these data, we chose epoxide 4, which potently restored the locomotor activity in MPTP-treated mice and efficiently penetrated the BBB, to further explore its potential mechanism of action. Epoxide 4 was found to robustly promote the survival of cultured dopamine neurons, protect dopamine neurons against toxin-induced degeneration, and trigger the mitogen-activated protein kinase (MAPK) signaling cascade in cells of neuronal origin. Meanwhile, neither the survival-promoting effect nor MAPK activation was observed in non-neuronal cells treated with epoxide 4. In the MPTP mouse model of Parkinson's disease, compound 4 increased the density of dopamine neuron fibers in the striatum, which can highlight its potential to stimulate striatal reinnervation and thus halt disease progression. Taken together, these data indicate that epoxide 4 can be a promising compound for further development, not only as a symptomatic but also as a neuroprotective and neurorestorative drug for Parkinson's disease.
  • Stotani, Silvia; Gatta, Viviana; Medda, Federico; Padmanaban, Mohan; Karawajzyk, Anna; Tammela, Päivi Sirpa Marjaana; Giordanetto, Fabrizio; Tzalis, Dimitrios; Collina, Simona (2018)
    Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.
  • Matovic, Jelena; Järvinen, Juulia; Bland, Helena C.; Sokka, Iris K.; Imlimthan, Surachet; Ferrando, Ruth Mateu; Huttunen, Kristiina M.; Timonen, Juri; Peräniemi, Sirpa; Aitio, Olli; Airaksinen, Anu J.; Sarparanta, Mirkka; Johansson, Mikael P.; Rautio, Jarkko; Ekholm, Filip S. (2020)
    Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.
  • Kaddouri, Yassine; Benabbes, Redouane; Ouahhoud, Sabir; Abdellattif, Magda; Hammouti, Belkheir; Touzani, Rachid (2022)
    Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure-activity relationship (SAR) interpretations for pharmacophore site predictions as (delta(-)center dot center dot center dot delta(-)), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (delta(-)center dot center dot center dot delta(-)) in common in N1---O4, whereas other compounds have only one delta(-) pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug-target interactions on this subject is currently underway.
  • Guo, Hui; Liu , Dongmei; Gao , Bin; Zhang, Xiaohui; You, Minli; Ren, Hui; Zhang, Hongbo; Almeida Santos, Helder; Xu , Feng (2016)
    Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.
  • Leino, Teppo O.; Turku, Ainoleena; Yli-Kauhaluoma, Jari Tapani; Kukkonen, Jyrki P.; Xhaard, Henri; Wallén, Erik A. A. (2018)
    A library of 70 000 synthetically accessible azulene-based compounds was virtually screened at the OX2 receptor. Based on the results, a series of azulene derivatives was synthesized and the binding to and activation of both orexin receptor subtypes were assessed. Two most promising binders were determined to have inhibition constants in the 3-9 mu M range and two other compounds showed weak OX2 receptor agonism. Furthermore, three compounds exhibited a concentration-dependent potentiation of the response to orexin-A at the OX1 but not the OX2 receptors. Altogether this data opens new approaches for further development of antagonists, agonists, and potentiators of orexin response based on the azulene scaffold. (C) 2018 Elsevier Masson SAS. All rights reserved.
  • Isenberg, Stefan; Weller, Stefan; Kargin, Denis; Valic, Srecko; Schwederski, Brigitte; Kelemen, Zsolt; Bruhn, Clemens; Krekic, Kristijan; Maurer, Martin; Feil, Christoph M.; Nieger, Martin; Gudat, Dietrich; Nyulaszi, Laszlo; Pietschnig, Rudolf (2019)
    Invited for this month's cover picture are the groups of Professors Rudolf Pietschnig at the University of Kassel, Professor Dietrich Gudat at the University of Stuttgart and Professor Laszlo Nyulaszi at the Budapest University of Technology and Economics. The cover picture shows the thermally induced homolytic cleavage of the central P-P bond in a phosphorus-rich bis-ferrocenophane furnishing P-centered radicals (as evidenced by the computed spin-density highlighted in blue). The central P-6 unit in the title compound is a structural analog of the connecting unit in Hittorf's violet phosphorus, which links the orthogonally arranged tubular entities. A portrait of the German physicist Johann Wilhelm Hittorf is included. Read the full text of their Full Paper at 10.1002/open.201900182.
  • Ravikumar, Balaguru; Timonen, Sanna; Alam, Zaid; Parri, Elina; Wennerberg, Krister; Aittokallio, Tero (2019)
    Owing to the intrinsic polypharmacological nature of most small-molecule kinase inhibitors, there is a need for computational models that enable systematic exploration of the chemogenomic landscape underlying druggable kinome toward more efficient kinome-profiling strategies. We implemented Virtual-KinomeProfiler, an efficient computational platform that captures distinct representations of chemical similarity space of the druggable kinome for various drug discovery endeavors. By using the computational platform, we profiled approximately 37 million compound-kinase pairs and made predictions for 151,708 compounds in terms of their repositioning and lead molecule potential, against 248 kinases simultaneously. Experimental testing with biochemical assays validated 51 of the predicted interactions, identifying 19 small-molecule inhibitors of EGFR, HCK, FLT1, and MSK1 protein kinases. The prediction model led to a 1.5-fold increase in precision and 2.8-fold decrease in false-discovery rate, when compared with traditional single-dose biochemical screening, which demonstrates its potential to drastically expedite the kinome-specific drug discovery process.
  • Valadbeigi, Younes; Kurten, Theo (2019)
    The interaction of H2SO4 with boron compounds including BH3, BF3, BCl3, BBr3, B(CN)(3) and B(OH)(3) was studied computationally using the omega B97xD density functional. All the BX3 compounds except B(OH)(3) bind to H2SO4 via both SOH center dot center dot center dot X hydrogen bonds, and interactions between the B atoms and the S=O oxygen atoms. B(OH)(3) interacts with H2SO4 solely through hydrogen bonds. B(CN)(3) and BCl3 exhibit the strongest and weakest interactions with H2SO4, respectively. Natural bond orbital (NBO) analysis shows that the relative weakness of the H2SO4- BCl3 interaction may be due to pi-bonding between the B and Cl atoms, and the occupation of the p(z) orbital of the B atom. The strong electron withdrawing groups CN in B(CN)(3) intensify electron deficiency of B atom and promote its tendency to capture electrons of oxygen atom of O=S group. Atoms in molecules (AIM) calculations show bond critical points (BCP) between the X groups of BX3 and the hydrogen atoms of H2SO4 for all cases except X = OH. Enthalpies and Gibbs free energies of deprotonation in the gas phase (Delta H-acid, Delta G(acid)) were calculated for (BX3)H2SO4 and (BX3)(2)H2SO4 complexes. These data revealed that clustering of BX3 with H2SO4 enhances the acidity of H2SO4 by about 9-58 kcal mol(-1). The (B(CN)(3))(2)H2SO4 cluster had Delta H-acid and Delta G(acid) values of 255.0 and 246.7 kcal mol(-1), respectively, and is the strongest Bronsted acids among the (BX3)(2)H2SO4 clusters.
  • Woiwode, Ulrich; Ferri, Martina; Maier, Norbert M.; Lindner, Wolfgang; Lämmerhofer, Michael (2018)
    Abstract A cardinal requirement for effective 2D-HPLC separations is sufficient complementarity in the retention profiles of first and second dimension separations. It is shown that retention and enantioselectivity of chiral selectors derived from cinchona alkaloids can be conveniently modulated by structural variation of the carbamate residue of the quinine/quinidine carbamate ligand of such chiral stationary phases (CSP). A variety of aliphatic and aromatic residues have been tested in comparison to non-carbamoylated quinine CSP. Various measures of orthogonality have been utilized to derive the CSP that is most complementary to the tert-butylcarbamoylated quinine CSP (tBuCQN CSP), which is commercially available as Chiralpak QN-AX column. It turned out that O-9-(2,6-diisopropylphenylcarbamoyl)-modified quinine is most promising in this respect. Its implementation as a complementary CSP for the separation of amino acids derivatized with Sanger’s reagent (2,4-dinitrophenylated amino acids) in the first dimension combined with a tBuCQN CSP in the second dimension revealed successful enantiomer separations in a comprehensive chiral×chiral 2D-HPLC setup. However, the degree of complementarity could be greatly enhanced when simultaneously the absolute configurations were exchanged from quinine to quinidine in the chiral selector of the first dimension separation resulting in opposite elution orders of the enantiomers in the two dimensions. The advantage of such a chiral×chiral over achiral×chiral 2D-HPLC setup, amongst others, is the perfect compatibility of the mobile phase because in both dimensions the identical eluent can be used.
  • Falke, J.; Parkkinen, J.; Vaahtera, L.; Hulsbergen-van de Kaa, C. A.; Oosterwijk, E.; Witjes, J. A. (2018)
    Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.
  • Freese, Tyll; Nieger, Martin; Namyslo, Jan C.; Schmidt, Andreas (2019)
    Sydnone imines were deprotonated with lithium bis(trimethylsilyl)amide at the C4 position to give the corresponding sydnone imine anions as lithium adducts. These can be represented as lithium stabilized anionic N-heterocyclic carbenes. Treatment with diisopropyl azodicarboxylate (DIAD) gave the corresponding C4 adducts, i.e. 4-hydrazinyl-sydnone imines, which form tautomers in solution. Reductive 1,3-dipolar cycloadditions of the sydnone imine anions with tetracyanoethylene (TCNE) resulted in the formation of pyrazoles, the mechanism of formation of which differs from known reactions. Reaction of the anion derived from the 2-methoxyphenyl sydnone imine with N,N-diisopropylcarbodiimide gave a ring-cleaved bisiminonitrile. Structure elucidations were accomplished by NMR spectroscopy and by four single crystal X-ray analyses. (C) 2019 Elsevier Ltd. All rights reserved.
  • Kolsi, Laura E.; Leal, Ana S.; Yli-Kauhaluoma, Jari; Liby, Karen T.; Moreira, Vânia M. (2018)
    Low 5-year survival rates, increasing incidence, as well as the specific challenges of targeting pancreatic cancer, clearly support an urgent need for new multifunctional drugs for the prevention and treatment of this fatal disease. Natural products, such as abietane-type diterpenoids, are widely studied as promiscuous anticancer agents. In this study, dehydroabietic oximes were identified as potential compounds to target pancreatic cancer and cancer-related inflammation. The compounds inhibited the growth of human pancreatic cancer Aspc-1 cells with IC50 values in the low micromolar range and showed anti-inflammatory activity, measured as the inhibition of nitric oxide production, an important inflammatory mediator in the tumour microenvironment. Further studies revealed that the compounds were able to induce cancer cell differentiation and concomitantly downregulate cyclin D1 expression with upregulation of p27 levels, consistent with cell cycle arrest at the G1 phase. Moreover, a kinase profiling study showed that one of the compounds has isoform-selective, however modest, inhibitory activity on RSK2, an AGC kinase that has been implicated in cellular invasion and metastasis.
  • Zippel, Christoph; Hassan, Zahid; Nieger, Martin; Bräse, Stefan (2020)
    A planar chiral dirhodium paddlewheel complex Rh-2(S-p-PCP)(4)based on the [2.2]paracyclophane has been synthesized for the challenging cyclopropanation of venylarene derivatives withtert-butyl alpha-diazo propionates. The homobimetallic rhodium catalyst relies on the high steric demand and rigidity of [2.2]paracyclophane that favors the cyclopropanation of 1-aryl substituted, 1,1-disubstituted and benzannulated alkenes over beta-hydride migration at room temperature with high diastereoselectivity.
  • Stahlberger, Mareen; Schwarz, Noah; Zippel, Christoph; Hohmann, Jens; Nieger, Martin; Hassan, Zahid; Brase, Stefan (2022)
    This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienayme three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.
  • Dytrtova, Jana Jaklova; Moslova, Karina; Jakl, Michal; Siren, Heli; Riekkola, Marja-Liisa (2021)
    Well-established label in biomolecules analysis, fluorescein isothiocyanate is commercially available in its two different isomers with equal fluorescence sensitivity, differing in meta- vs. para-isothiocyanate position. It was found in this study that the stability of the isomers depends on the polarity of different solvents and the pyridine (stabiliser) presence. The lowest stability has fluorescein isothiocyanate in water solvent. In acidic solution, their quinoid (acid) form switches to the lactone form. The p-quinoid form has higher tendency to create dimers and trimers and is less soluble in acetone than the lactone form. [GRAPHICS] .