1020-16-2Relevant articles and documents
Identification of dual Sigma1 receptor modulators/acetylcholinesterase inhibitors with antioxidant and neurotrophic properties, as neuroprotective agents
Rui, Marta,Rossino, Giacomo,Coniglio, Stefania,Monteleone, Stefania,Scuteri, Arianna,Malacrida, Alessio,Rossi, Daniela,Catenacci, Laura,Sorrenti, Milena,Paolillo, Mayra,Curti, Daniela,Venturini, Letizia,Schepmann, Dirk,Wünsch, Bernhard,Liedl, Klaus R.,Cavaletti, Guido,Pace, Vittorio,Urban, Ernst,Collina, Simona
, p. 353 - 370 (2018)
In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RRC-33, a S1R modulator developed by us, donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant compound with neuroprotective properties. A small library of compounds was synthesized and preliminary in vitro screening performed. Some compounds showed good S1R binding affinity, selectivity towards S2R and N-Methyl-D-Aspartate (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by evaluating their protective effect against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Tested compounds resulted effective in decreasing ROS production, thus ameliorating the cellular survival. Moreover, compounds 10 and 20 showed to be effective in promoting the neurite elongation of Dorsal Root Ganglia (DRG), thus demonstrating a promising neurotrophic activity. Of note, the tested compounds did not show any cytotoxic effect at the concentration assayed. Relying on these encouraging results, both compounds will undergo a structure optimization program for the development of therapeutic candidates for neurodegenerative diseases treatment.
Synthesis of 4-(3-oxo-3-phenylpropyl)morpholin-4-ium chloride analogues and their inhibitory activities of nitric oxide production in lipopolysaccharide-induced BV2 cells
Yoon, Sung-Hwa,Lee, Eunhwa,Cho, Duk-Yeon,Ko, Hyun Myung,Baek, Ha Yeon,Choi, Dong-Kug,Kim, Eunha,Park, Ju-Young
supporting information, (2021/02/02)
Based on our previous report that 3-morpholino-1-phenylpropan-1-one 2, one of the fluoxetine's simplified morpholino analogue, inhibited nitric oxide (NO) production, in this paper, various substituted benzene analogues with morpholine hydrochloride of 2 were synthesized and their inhibitory effects on NO production in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 2-trifluoromethyl analogue 16n (IC50 = 8.6 μM) showed a significantly higher inhibitory activity than that of the parent compound 2a (IC50 > 50 μM) and suppressed NO production dose-dependently without cytotoxicity. Compound 16n also inhibited iNOS expression in LPS-induced BV2 cells at 2, 10 and 20 μM concentrations. These results suggest that compound 16n inhibited NO production by suppressing the expression of iNOS and can be used as a lead structure for developing new inhibitor of NO production.
An efficient water-mediated synthetic route for the alkylation of heteroarenes
Seyi?Tdanlio?lu, P?nar,Hanashalshahaby, Essam Hamied Ahmed,ünalero?lu, Canan
, p. 1598 - 1610 (2019/01/03)
An efficient synthetic route has been described for the alkylation of 1H-indole, 1H-benzimidazole, and 1H-benzotriazole. This approach features the alkylation of heteroaromatics through in situ generated enones from ketonic Mannich bases under metal-free conditions. A series of alkylated heteroaromatics have been synthesized via the K10 catalyzed alkylation reactions of these heteroaromatics with a variety of ketonic Mannich bases. Environmentally benign K10 catalyst, water-mediated mild reaction conditions, and the efficient synthesis of alkylated products are the advantages of this alkylation method.
