5394-18-3Relevant articles and documents
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.
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.
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).
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.
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).
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.
