5394-18-3Relevant academic research and scientific papers
Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors
Jarończyk, Ma?gorzata,Wo?osewicz, Karol,Gabrielsen, Mari,Nowak, Gabriel,Kufareva, Irina,Mazurek, Aleksander P.,Ravna, Aina W.,Abagyan, Ruben,Bojarski, Andrzej J.,Sylte, Ingebrigt,Chilmonczyk, Zdzis?aw
, p. 200 - 210 (2012)
It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquifex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators.
Development of a Modified Julia Olefination of Imides for the Synthesis of Alkaloids
Trinh, Huu Vinh,Perrin, Lionel,Goekjian, Peter G.,Gueyrard, David
, p. 2944 - 2953 (2016)
We report the development of the intramolecular Julia olefination of imides. This original reaction produces N-fused bicyclic enamide compounds, which are interesting precursors in the synthesis of alkaloids. We show that this transformation enables access to [5,6], [6,5], and [6,6] fused bicyclic lactam enamides. The scope and the limitations of the reaction are presented as well as computational studies concerning novel mechanistic aspects of the title reaction.
A Model for Nicotinamide-Tryptophane Charge-Transfer Interactions: the Complexation of Nicotinamide-Ammonium Salts by a Macrocyclic Receptor Molecule Bearing Tryptophane Side Chains
Behr, Jean-Paul,Lehn, Jean-Marie
, p. 2112 - 2118 (1980)
The complexation of primary ammonium salt substrates by macrocyclic polyether receptor molecules provides a general method for studying the nature and stereochemistry of intermolecular interactions.The substrates and receptors are fitted with one of the interacting units and the resulting effects in the complex are analyzed.The method is used to study the biologically important indole-pyridinium donor-acceptor interaction.The complexes between macrocycles, bearing an indole group in side chains, and pyridinium-ammonium salts display a characteristic charge-transfer band.The absorption coefficients and stability constants have been determined.Competition experiments also provide a new method for measuring the stability constants of macrocycle-ammonium complexes in organic solvents.
Design and synthesis of H2S-donor hybrids: A new treatment for Alzheimer's disease?
Sestito, Simona,Pruccoli, Letizia,Runfola, Massimiliano,Citi, Valentina,Martelli, Alma,Saccomanni, Giuseppe,Calderone, Vincenzo,Tarozzi, Andrea,Rapposelli, Simona
, (2019)
Hydrogen sulphide (H2S) is an endogenous gasotransmitter, largely known as a pleiotropic mediator endowed with antioxidant, anti-inflammatory, pro-autophagic, and neuroprotective properties. Moreover, a strong relationship between H2S and aging has been recently identified and consistently, a significant decline of H2S levels has been observed in patients affected by Alzheimer's disease (AD). On this basis, the use of H2S-donors could represent an exciting and intriguing strategy to be pursued for the treatment of neurodegenerative diseases (NDDs). In this work, we designed a small series of multitarget molecules combining the rivastigmine-scaffold, a well-established drug already approved for AD, with sulforaphane (SFN) and erucin (ERN), two natural products deriving from the enzymatic hydrolysis of glucosinolates contained in broccoli and rocket, respectively, endowed both with antioxidant and neuroprotective effects. Notably, all new synthetized hybrids exhibit a H2S-donor profile in vitro and elicit protective effects in a model of LPS-induced microglia inflammation. Moreover, a decrease in NO production has been observed in LPS-stimulated cells pre-treated with the compounds. Finally, the compounds showed neuroprotective and antioxidant activities in human neuronal cells. The most interesting compounds have been further investigated to elucidate the possible mechanism of action.
Synthesis of diosgenyl quaternary ammonium derivatives and their antitumor activity
Xia, Xi,Chen, Yu,Wang, Lin,Yang, Zhi-Gang,Ma, Xiao-Dong,Zhao, Zhi-Gang,Yang, Hong-Jun
, (2021)
Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte).
Biacore biosensor immunoassay for 4-nonylphenols: Assay optimization and applicability for shellfish analysis
Samsonova, Jeanne V.,Uskova, Natalya A.,Andresyuk, Alexey N.,Franek, Milan,Elliott, Christopher T.
, p. 975 - 985 (2004)
A rapid Biacore biosensor immunoassay of 4-nonylphenols was developed. Two types of antibodies were used in the study: polyclonal antibodies with high cross-reactivity towards technical 4-nonylphenol and a monoclonal antibody very specific to 4-n-nonylphenol. 9-(p-Hydroxyphenyl)nonanoic acid was immobilized onto surface of a sensor chip. The best assay sensitivity was achieved using a flow rate of 50 μl min-1 and injection time of 2 min. For the assay incorporating monoclonal antibodies a limit of detection 2 ng ml -1 for 4-n-nonylphenol was achieved. With polyclonal antibodies one order lower sensitivity was observed for 4-nonylphenols. High background level of calibration curve for technical 4-nonylphenol was decreased by using IgG fraction of polyclonal antibodies in combination with lower amount of immobilised 9-(p-hydroxyphenyl)nonanoic acid. Sensitivity of the assay was improved by using a chip with a new derivative on a surface-N-aminobutyl [2-(4-hydroxyphenyl)ethylamine] (limit of detection - 5 ng ml-1). Applicability of the developed assays to ecological monitoring was checked in experiments using shellfish samples. 4-n-Nonylphenol from spiked samples was extracted into hexane followed by clean-up on NH2 SPE columns. Calibration curves generated for cockles, mussels and oyster samples were identical (limit of detection about 10 ng g-1) whereas for scallop samples a slight decrease (about 5-10%) of absolute response was observed. In the assay using the monoclonal antibody specific to 4-n-nonylphenol 31 shellfish samples were found to be negative. Results obtained with polyclonal antibodies indicated that two scallop samples contained a quantity of 4-nonylphenols. The developed biosensor assay could be applied for shellfish analysis as a preliminary screening method.
Synthesis of New 1,2,3-Triazolo-naphthalimide/phthalimide Conjugates via ‘Click’ Reaction: DNA intercalation and cytotoxic studies
Shankaraiah, Nagula,Kumar, Niggula P.,Tokala, Ramya,Gayatri, Bulusu S.,Talla, Venu,Santos, Leonardo S.
, p. 454 - 461 (2019)
Cancer is a complex disease which involves abnormalities of multiple cellular pathways. Current chemotherapeutic drugs are mainly designed to target the DNA and cell division. Therefore, in the present study, we have synthesized a new series of 1,2,3-triazolo-naphthalimide/phthalimide conjugates and evaluated their in vitro cytotoxicity against selected human cancer cells. Among the tested compounds, one of them displayed notable cytotoxic activity against A549 lung cancer cells with an IC50 (half maximal inhibitory concentration) value of 7.6 ± 0.78 μM. To determine the effect of this compound on cell viability, acridine orange/ethidium bromide (AO/EB) and 4’,6-diamidino-2-phenylindole (DAPI) staining studies were performed. These apoptotic features were clearly indicating that the compound inhibited cell proliferation by apoptosis. Further, relative viscosity measurements and molecular docking studies with the most three active compounds indicated that these new compounds bind to DNA by intercalation.
Design, synthesis and preliminary bioactivity evaluation of bitopic benzopyranomorpholine analogues as selective dopamine D3 receptor ligands as anti-drug addiction therapeutic agents
Cai, Jin,Chen, Xixi,Huang, Mingqi,Ji, Min,Wang, Yuhong
, (2021/08/09)
Three series of bitopic benzopyranomorpholine analogues were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine D3 receptor. Binding affinities of target compounds were determined using the method of radioligand binding assay. Most compounds demonstrated considerable binding affinities and selectivity for D3 receptor. Besides, the compounds were screened for their ability to alleviate withdrawal symptoms of opioid addiction in animal behavioral models. The results showed that compound 20h displayed nanomolar affinity for the D3R, and exhibited anti-drug addiction efficacy in the animal model of of naloxone-induced withdrawal symptoms in morphine-dependent mice.
Strategic engineering of alkyl spacer length for a pH-tolerant lysosome marker and dual organelle localization
Bhowal, Rohit,Biswas, Suprakash,Chopra, Deepak,Dutta, Tanoy,Koner, Apurba L.,Silswal, Akshay
, p. 9630 - 9644 (2021/07/28)
Long-term visualization of lysosomal properties is extremely crucial to evaluate diseases related to their dysfunction. However, many of the reported lysotrackers are less conducive to imaging lysosomes precisely because they suffer from fluorescence quenching and other inherent drawbacks such as pH-sensitivity, polarity insensitivity, water insolubility, slow diffusibility, and poor photostability. To overcome these limitations, we have utilized an alkyl chain length engineering strategy and synthesized a series of lysosome targeting fluorescent derivatives namelyNIMCsby attaching a morpholine moiety at theperiposition of the 1,8-naphthalimide (NI) ring through varying alkyl spacers between morpholine and 1,8-naphthalimide. The structural and optical properties of the synthesizedNIMCswere explored by1H-NMR, single-crystal X-ray diffraction, UV-Vis, and fluorescence spectroscopy. Afterward, optical spectroscopic measurements were carefully performed to identify a pH-tolerant, polarity sensitive, and highly photostable fluoroprobes for further live-cell imaging applications.NIMC6displayed excellent pH-tolerant and polarity-sensitive properties. Consequently, allNIMCswere employed in kidney fibroblast cells (BHK-21) to investigate their applicability for lysosome targeting and probing lysosomal micropolarity. Interestingly, a switching of localization from lysosomes to the endoplasmic reticulum (ER) was also achieved by controlling the linker length and this phenomenon was subsequently applied in determining ER micropolarity. Additionally, the selected probeNIMC6was also employed in BHK-21 cells for 3-D spheroid imaging and inCaenorhabditis elegans(C. elegans) forin vivoimaging, to evaluate its efficacy for imaging animal models.
Antioxidant activity of two edible isothiocyanates: Sulforaphane and erucin is due to their thermal decomposition to sulfenic acids and methylsulfinyl radicals
Cedrowski, Jakub,D?browa, Kajetan,Przybylski, Pawe?,Krogul-Sobczak, Agnieszka,Litwinienko, Grzegorz
, (2021/03/30)
Sulforaphane (SFN) and erucin (ERN) are isothiocyanates (ITCs) bearing, respectively, methylsulfinyl and methylsulfanyl groups. Their chemopreventive and anticancer activity is attributed to ability to modulate cellular redox status due to induction of Phase 2 cytoprotective enzymes (indirect antioxidant action) but many attempts to connect the bioactivity of ITCs with their radical trapping activity failed. Both ITCs are evolved from their glucosinolates during food processing of Cruciferous vegetables, therefore, we studied antioxidant behaviour of SFN/ERN at elevated temperature in two lipid systems. Neither ERN nor SFN inhibit the oxidation of bulk linolenic acid (below 100 °C) but both ITCs increase oxidative stability of soy lecithin (above 150 °C). On the basis of GC-MS analysis we verified our preliminary hypothesis (Antioxidants 2020, 9, 1090) about participation of sulfenic acids and methylsulfinyl radicals as radical trapping agents responsible for the antioxidant effect of edible ITCs during thermal oxidation of lipids at elevated temperatures (above 140 °C).
