Biological evaluation of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as inhibitors of LPS-induced TNF- alpha secretion

This study describes the effect of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as tumor necrosis factor alpha (TNF-á) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-á secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo [1,2-c] quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo [1,2-c] quinazoline derivatives may have a potential as anti-inflammatory agent

A synthethic overview of new molecules with 5-HT 1A binding affinities

The present review discusses the synthetic strategies of new ligands exhibiting mainly 5-HT1A binding affinities. Specifically we focused our attention in the synthesis of compounds structurally telated to arylpiperazine, 2-aminotetralin, and benzopyran derivatives

Synthesis of 2-benzothienyl carbonyl 4-arylpiperazines as novel delavirdine analogs

A novel series of 2-benzothienyl carbonyl arylpiperazines (6a-f) was synthesized as potential HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs). Preparation of the derivatives was performed by reacting benzo[b]thiophene carbonyl chloride (5) with a series of substituted 4-arylpiperazines

Synthesis of benzo[b]thiophene carboxamides connected to 4-arylpiperazines through a benzylic spacer: Potential Ligands with 5-HT1A binding affinity

New benzothiophene arylpiperazine derivatives 8 (a-f) were synthesized as potential serotoninergic agents with 5-HT1A receptor affinity. Preparation of the derivatives was performed by treating N-[2-(chloromethyl)phenyl]-4,7-dimethoxybenzo[b]thiophene-2-carboxamide (7) with a series of substituted 4-arylpiperazines

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D-2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 +/- 0.82 nM, and 13c, Ki = 6.85 +/- 0.19 nM, showed the highest potencies. The affinities for D-2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D-2 receptor in the nanomolar range (7n: Ki = 307 +/- 6 nM and 7m: Ki = 593 +/- 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D-2 receptor (D-2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q(2) = 0.625, 0.523 for CoMFA and CoMSIA and r(ncv)(2) = 0.967, 0.959 for CoMFA and CoMSIA, respectively).Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1170269 1170662 3180602 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT

NADPH oxidase activity: Spectrophotometric determination of superoxide using pyrogallol red

© 2017 Elsevier Inc.A simple and fast spectrophotometric methodology able to quantify superoxide released by NADPH oxidase from differentiated promyelocytic leukaemia (HL-60) cells using pyrogallol red is described.The latter is based on the known stoichiometry of the reaction between superoxide and pyrogallol red and the inability of pyrogallol red to react with hydrogen peroxide. In addition, we developed a 96-wells microplate-based method able to determine NADPH oxidase activity. Using this method, we determined pharmacological properties of the NADPH oxidase inhibitors VAS2870 and diphenyleneiodonium and the obtained IC50 values were in good agreement with previous reported data. NOX2 is highly expressed in differentiated promyelocytic leukaemia cells, whereas other isoforms are not detected or expressed at low amounts. Likewise, this methodology may be a useful assay for NOX2 inhibitor screening. NADPH oxidases are involved in several physiological and pathological processes, ren