Search results for "Molecular modelling"

Leptin and the OB-receptor as anti-obesity target: recent in silico advances in the comprehension of the protein-protein interaction and rational dru…

2014

The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works b…

Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.

2020

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Molecular modelling studies on dopamine-amino acid conjugates as potential dopaminergic modulators

2015

Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and m…

2019

Abstract Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory…

Recent advances on CDK inhibitors: An insight by means of in silico methods

2017

The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…

Molecular modelling and QSAR in the discovery of HIV-1 integrase inhibitors

2007

The treatment regimens for the HIV-1 have mainly included reverse transcriptase or protease inhibitors but their long-term clinical utility is limited by severe side effects and viral drug resistance. A new attractive target for chemotherapeutic intervention can be the Integrase enzyme, that mediates the integration of HIV-1 DNA into a host chromosome, for which there is no known counterparts in the host cell. A number of derivatives have been found to inhibit IN in in vitro assays, but no successful drug based on them has emerged so far, although many compounds have been proposed. Moreover most of the inhibitors do not belong to a very precise structural class: this fact makes these compou…

Cobalt complex based on cyclam for reversible binding of nitric oxide

2008

We report the synthesis and theoretical calculations of nitrosyl cobalt complexes based on saturated tetraazamacrocycle for the reversible binding of nitric oxide (NO). Density-functional theory provides a rigorous theoretical framework for analysing, interpreting and investigating important parameters in order to further tune the properties of these complexes to the target application. We focus on understanding the stability of complexes in methanol solution as well as their reactivity and stability evolution in the presence of NO, O2 and higher nitrogen oxides intermediates. Calculations have been used to explore appropriate combinations of different macrocycles, metal centres and ligands…

3D-QSAR study of ligands for two human olfactory receptors

2008

International audience; All living organisms, including human beings, are able to detect and discriminate myriads of structurally diverse odorants through their interaction with olfactory receptors (ORs) (1). It is well accepted that the perception of thousands of odors by about 380 ORs results from a combinatorial coding, in which one OR recognizes multiple odorants and different odorants are recognized by different combinations of ORs (2). In a previous study (3), the functional characterization on two human ORs, called OR1G1 (class II) and OR52D1 (class I) have been performed using 95 odorant molecules. We used these previously obtained functional data (3) to perform a molecular modellin…