Littérature scientifique sur le sujet « Cyclocurcumin »

The photoisomerization process of a biomimetic cyclocurcumin derivative is explored by molecular modelling. It presents enhanced capabilities respect to natural cyclocurcumin in terms of isomerization, TPA and environment dependency.

Although identical in molecular formula and weight, curcumin and cyclocurcumin show remarkable differences in their reactivity. Both are natural compounds isolated from the rhizome of turmeric, the former is involved in the diketo/keto-enol tautomerism through the bis-α,β-unsaturated diketone unit according to the polarity of the solvent, while the latter could react by trans-cis isomerization due to the presence of the α,β-unsaturated dihydropyranone moiety. Even if curcumin is generally considered responsible of the therapeutical properties of Curcuma longa L. due to its high content, cyclocurcumin has attracted great interest over the last several decades for its individual behavior and specific features as a bioactive compound. Cyclocurcumin has a hydrophobic nature characterized by fluorescence emission, solvatochromism, and the tendency to form spherical fluorescent aggregates in aqueous solution. Molecular docking analysis reveals the potentiality of cyclocurcumin as antioxidant, enzyme inhibitor, and antiviral agent. Promising biological activities are observed especially in the treatment of degenerative and cardiovascular diseases. Despite the versatility emerging from the data reported herein, the use of cyclocurcumin seems to remain limited in clinical applications mainly because of its low solubility and bioavailability.

Background: Human Swine flu is a viral disease caused by Influenza A virus, an orthomyxovirus, contains the glycoprotein neuraminidase described as H1N2. Neuraminidase, a glycoside hydrolase enzyme assist in budding from the host cells. The medicines available for the treatment of swine flu are Oseltamivir and Zanamivir acting against glycoproteins, mainly haemagglutinin and neuraminidase. Ayurvedic medicinal system described many herbs which acts as antiviral and among that Curcumin, Bisdemethoxycurcumin, Cyclocurcumin, Ascorbic Acid and Eugenol have been selected based on their potential antiviral properties. Objective: This study aims to provide the interaction between Curcumin, Bisdemethoxycurcumin, Cyclocurcumin, Ascorbic Acid and Eugenol (herbal molecules) against influenza A virus by targeting Neuraminidase. Methods: The selected protein target (1NN2.pdb) of swine flu (neuraminidase) was downloaded from Protein Data Bank with resolution 2.2 A0. The ligands (Curcumin, Cyclocurcumin, Bisdemethoxycurcumin, Ascorbic acid, Eugenol and Zanamvir) for the docking study have been download form PubChem database. The present study has been performed using docking simulation with the help of AutoDock Vina. Results: Result shows that the Curcumin, Bisdemethoxycurcumin and Cyclocurcumin is showing good binding affinity with target protein, Nuraminidase as compared to known drug Zanamivir and other selected ligands (Eugenol, Ascorbic Acid). The docking energy values varies between -4.9 to -7.5 Kcal/mole. Conclusion: The present study has shown that the Curcumin, Bisdemethoxycurcumin and Cyclocurcumin showing good binding affinity with target protein, Nuraminidase as compared to known binder Zanamivir and other selected ligands (Eugenol, Ascorbic Acid). Curcumin and their derivatives (Bisdemethoxycurcumin, Cyclocurcumin) based drugs may act singly or synergistically along with other known drugs and prove to be more effective for influenza type A treatment.

Solvent effects determine the fate of cyclocurcumin photochemistry: in non-polar environments fluorescence is preferred, while in polar solvents the photoisomerization path is opened, paving the way to applications as chemosensors and for theranostic purposes.

The study of fast non-equilibrium solvent relaxation in organic chromophores is still challenging for molecular modeling and simulation approaches, and is often overlooked, even in the case of non-adiabatic dynamics simulations. Yet, especially in the case of photoswitches, the interaction with the environment can strongly modulate the photophysical outcomes. To unravel such a delicate interplay, in the present contribution we resorted to a mixed quantum–classical approach, based on quantum mechanically derived force fields. The main task is to rationalize the solvent reorganization pathways in chromophores derived from cyclocurcumin, which are suitable for light-activated chemotherapy to destabilize cellular lipid membranes. The accurate and reliable decryption delivered by the quantum-derived force fields points to important differences in the solvent’s reorganization, in terms of both structure and time scale evolution.

Au-delà de la thérapie photodynamique (PDT), il existe plusieurs alternatives thérapeutiques assistées par la lumière parmi lesquelles la thérapie photothermique (PTT) ou encore la photoisomérisation dont l’action mécanique induirait des dommages cellulaires au sein des membranes. De plus, les molécules capables d’absorber simultanément deux photons permettraient de surmonter la nécessité d’une excitation à haute énergie par photon tout en gardant une pénétration suffisante des tissus. Dans ce contexte, nous nous sommes intéressés à la conception et à l’étude d’analogues biomimétiques de la cyclocurcumine (CC), un photoswitch E/Z naturel. Guidé par la modélisation moléculaire, ces nouveaux composés de type donneur-accepteur ont été structurellement conçus pour accroître la section efficace d'absorption à deux photons (σ2). Dans un premier temps, nous avons synthétisé deux classes d’analogues de la CC portant des groupements accepteurs (oxo et malonitrile) et donneurs (hydroxy, alcoxy et amine) ainsi qu’un bras PEG pour augmenter leur hydrophilie. Libres en solution, les dérivés oxo subissent une isomérisation photoinduite réversible, sans aucune isomérisation thermique en retour dans l’obscurité alors que les dérivés malonitrile ne photocommutent plus mais subissent une relaxation vibrationnelle. Elle conduit ainsi à une augmentation de température, d’intérêt en thérapie photothermique. Enfin, confinées dans un environnement lipidique (bicouches de liposomes et monocouches de Langmuir), la cinétique d’isomérisation directe E→Z des composés oxo est fortement ralentie et aucune isomérisation retour Z→E n’est observée, ni thermique ni sous illumination. Ces mêmes composés ont montré une efficacité certaine pour perturber la fluidité membranaire, plus ou moins prononcée selon la forme, Z ou E, la longueur de la chaîne alcoxy ou encore la présence du motif PEG. Les dérivés malonitrile quant à eux se voient diminuer leur effet photothermique au sein des bicouches lipidiques, après plusieurs cycles d’irradiation. L’ensemble de cette étude est une preuve de concept quant au potentiel des réponses photoinduites des analogues de la cyclocurcumine pour la perturbation de la fluidité membranaire vers une potentielle utilisation in vivo
Beyond photodynamic therapy (PDT), there are several light-assisted therapeutic alternatives, including photothermal therapy (PTT) and photoisomerization, whose mechanical action would induce cellular damage within the membranes. Also, molecules able to simultaneously absorb two photons would overcome the need for high energy excitation per photon while maintaining sufficient tissue penetration. In this context, we were interested in designing and studying biomimetic analogues of cyclocurcumin (CC), a natural E/Z photoswitch. Guided by molecular modeling, those novel donor-acceptor compounds were structurally designed to increase the effective two-photon absorption cross section (σ2).First, we synthesized two classes of CC analogues bearing acceptor (oxo and malonitrile) and donor (hydroxy, alkoxy and amine) groups as well as a PEG arm to increase their hydrophilicity. Free in solution, the oxo derivatives show a reversible photoinduced isomerization, without any thermal isomerization in the dark, whereas the malonitrile derivatives do not photoswitch but undergo a vibrational relaxation. This is leading to a temperature increase, of interest in photothermal therapy. Finally, confined in a lipidic environment (liposomes bilayers and Langmuir monolayers), the direct E→Z isomerization kinetics of oxo compounds is strongly slowed down and no Z→E back isomerization is observed. Those compounds also showed a certain efficiency to disrupt membrane fluidity, more or less pronounced depending on the form, Z or E, the length of the alkoxy chain or the presence of the PEG unit. The malonitrile derivatives exhibit a diminished photothermal effect in lipid bilayers after several irradiation cycles.Taken together, this study is a proof of concept for the potential of photoinduced responses of cyclocurcumin analogs for disruption of membrane fluidity towards potential use in vivo