Design, synthesis, and antiproliferative effect of 2,9-bis[4-(pyridinylalkylaminomethyl)phenyl]-1,10-phenanthroline derivatives on human leukemic cells by targeting G-quadruplex.

Current multiagent chemotherapy regimens have improved the cure rate in acute leukemia patients, but they are highly toxic and poorly efficient in relapsed patients. To improve the treatment approaches, new specific molecules are needed. The G-quadruplexes (G4s), which are noncanonical nucleic acid structures found in specific guanine-rich DNA or RNA, are involved in many cellular events, including control of gene expression.

Emotional Processing in Healthy Ageing, Mild Cognitive Impairment, and Alzheimer's Disease.

Emotional processing, particularly facial expression recognition, is essential for social cognition, and dysfunction may be associated with poor cognitive health. In pathological ageing conditions, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD), in which cognitive impairments are present, disturbed emotional processing and difficulty with social interactions have been documented. However, it is unclear how pathological ageing affects emotional processing and human social behaviour.

Verbal emotional memory laterality effect on amygdalohippocampectomy for refractory epilepsy.

Objectives: To study the brain lateralization of the verbal emotional memory and the influence of the emotional valence, we investigated a sample composed of patients with medial temporal lobe refractory epilepsy (MTLE) treated with unilateral amygdalohippocampectomy compared to a control group.

Materials & Methods: A new task (Verbal Association) was designed and implemented to assess emotional memory performance. It was applied to 62 patients with MTLE of whom 31 have been subjected to right amygdalohippocampectomy and 31 to left amygdalohippocampectomy.

Arsenic removal from natural groundwater using 'green rust': Solid phase stability and contaminant fate.

Arsenic (As) contamination in groundwater remains a pressing global challenge. In this study, we evaluated the potential of green rust (GR), a redox-active iron phase frequently occurring in anoxic environments, to treat As contamination at a former wood preservation site. We performed long-term batch experiments by exposing synthetic GR sulfate (GR) to As-free and As-spiked (6 mg L) natural groundwater at both 25 and 4 °C.

Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives.

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated against three protozoan parasites (, , and ). Biological results showed antiprotozoal activity with IC values in the µM range. In addition, the cytotoxicity of these original molecules was assessed with human HepG2 cells.

Design, Synthesis and Biological Evaluation of New Substituted Diquinolinyl-Pyridine Ligands as Anticancer Agents by Targeting G-Quadruplex.

G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents.

Design, synthesis, and antiprotozoal evaluation of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives.

A series of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives was synthesized, and the compounds were screened in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiparasitic activity with IC values in the μm range. The in vitro cytotoxicity of these molecules was assessed by incubation with human HepG2 cells; for some derivatives, cytotoxicity was observed at significantly higher concentrations than antiparasitic activity.

Synthesis and Antiproliferative Effect of Ethyl 4-[4-(4-Substituted Piperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxalinecarboxylate Derivatives on Human Leukemia Cells.

Acute leukemia is a hematological malignancy with high incidence and recurrence rates and is characterized by an accumulation of blasts in bone marrow due to proliferation of immature lymphoid or myeloid cells associated with a blockade of differentiation. The heterogeneity of leukemia led us to look for new specific molecules for leukemia subtypes or for therapy-resistant cases. Among heterocyclic derivatives that attracted attention due to their wide range of biological activities, we focused our interest on the pyrrolo[1,2-a]quinoxaline heterocyclic framework that has been previously identified as an interesting scaffold for antiproliferative activities against various human cancer cell lines.

Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives.

Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile.

Design, Synthesis, and Evaluation of 2,9-Bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline Derivatives as G-Quadruplex Ligands.

Genomic sequences able to form guanine quadruplexes (G4) are found in oncogene promoters, in telomeres, and in 5'- and 3'-untranslated regions as well as introns of messenger RNAs. These regions are potential targets for drugs designed to treat cancer. Herein, we present the design and syntheses of ten new phenanthroline derivatives and characterization of their interactions with G4-forming oligonucleotides.

Diminished oligomerization in the synthesis of new anti-angiogenic cyclic peptide using solution instead of solid-phase cyclization.

The design and synthesis of novel peptides that inhibit angiogenesis is an important area for anti-angiogenic drug development. Cyclic and small peptides present several advantages for therapeutic application, including stability, solubility, increased bio-availability and lack of immune response in the host cell. We describe here the synthesis and biological evaluations of a new cyclic peptide analog of CBO-P11: cyclo(RIKPHE), designated herein as CBO-P23M, a hexamer peptide encompassing residues 82 to 86 of VEGF which are involved in the interaction with VEGF receptor-2.

Discrimination and categorization of emotional facial expressions and faces in Parkinson's disease.

Our objective was to compare the ability to discriminate and categorize emotional facial expressions (EFEs) and facial identity characteristics (age and/or gender) in a group of 53 individuals with Parkinson's disease (PD) and another group of 53 healthy subjects. On the one hand, by means of discrimination and identification tasks, we compared two stages in the visual recognition process that could be selectively affected in individuals with PD. On the other hand, facial expression versus gender and age comparison permits us to contrast whether the emotional or non-emotional content influences the configural perception of faces.

Design, characterization, and evaluation of peptide arrays allowing the direct monitoring of MMP activities.

Characterization of matrix metalloprotease (MMP) activities is of increasing interest for cancer prognosis or treatment follow-up. Indeed, MMP-1, -2 and -9 are widely involved in the growth of many tumors and progression steps such as angiogenesis, invasion, and metastasis. Fluorogenic peptide MMP substrates were previously synthesized with the aim of detecting MMP activities.

Differential regional brain responses to induced maternal behavior in rats measured by cytochrome oxidase immunohistochemistry.

Maternal behavior (MB) in rats is expressed under neural control of vomeronasal structures. Some of these regions exert an inhibitory role, such as the accessory olfactory bulb (AOB), while others exert an excitatory role, such as the medial preoptic area (MPOA). In previous studies, using 2-DG as a marker for neuron activity at neuron terminal level, we reported that AOB showed a decrease and MPOA an increase when compared with control rats (non-exposed to pups) during the display of MB.

Gut-brain chemokine changes in portal hypertensive rats.

Background: Hepatic encephalopathy is a syndrome whose physiopathology is poorly understood; therefore, current diagnostic tests are imperfect and modern therapy is nonspecific. Particularly, it has been suggested that inflammation plays an important role in the pathogenesis of portal hypertensive encephalopathy in the rat.

Aim: We have studied an experimental model of portal hypertension based on a triple partial portal vein ligation in the rat to verify this hypothesis.

Portal hypertension in 18-month-old rats: memory deficits and brain metabolic activity.

Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. We compared the performance of 18-month-old prehepatic portal hypertensive rats (PH) and 18-month-old normal rats (CO) in spatial short-term and reference memory tasks in the Morris water maze and in active avoidance task. The PH group showed worse spatial short-term memory than the CO group.

Perception and recall of faces and facial expressions following temporal lobectomy.

The perception of and memory for faces, with or without emotional content, were studied in 43 patients with temporal lobe epilepsy who had undergone unilateral resection of the hippocampus and the amygdala and in 43 healthy participants for comparison. Each participant performed four tasks from the Florida Affect Battery (Facial Discrimination, Affect Discrimination, Affect Naming, Affect Selection) and two memory tasks (in one case of a face and in the other of a facial expression). Findings indicated that, although patients with unilateral temporal lobectomy (right or left) showed no difficulty in discriminating faces, they were not as good at remembering faces.

The role of the amygdala in facial emotional expression during a discrimination task.

A total of 50 patients with temporal lobe epilepsy with unilateral resection of the hippocampus and the amygdala were studied: --27 with left lobectomy (LTL group) and 23 with right lobectomy (RTL group)--; and 28 healthy control participants (HC group). The task consisted of identifying the dissimilar photograph from a group of photographs of the same face. The difference could correspond to the identity of the model or the facial expression (happiness, anger, sadness and fear).

Hippocampal and caudate metabolic activity associated with different navigational strategies.

Hippocampal and striatal systems are widely related to spatial tasks. Depending on the strategies used, different memory systems can be activated. In this study, the authors used the cytochrome c-oxidase technique as a functional marker of the hippocampal and dorsal striatum activity related to training in several water maze tasks.