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Exploring the molecular structure, vibrational spectroscopic, quantum chemical calculation and molecular docking studies of curcumin: A potential PI3K/AKT uptake inhibitor.

ABSTRACT: The IUPAC name of curcumin is (1E, 6E)-1,7-Bis(4-hydroxy-3methoxyphenyl) hepta-1,6-e-3,5-dione (7B3M5D) and is characterized by spectroscopic profiling with FT-IR and FT-Raman spectra obtained both experimentally and theoretically. PED analysis was done for the confirmation of minimum energy obtained in the title compound. Optimized geometrical parameters are compared with experimental values obtained for 7B3M5D by utilizing B3LYP functional employing 6-311++G (d,p) level of theory. The HOMO-LUMO, MEP, and Fukui function analysis has been used to elucidate the information regarding charge transfer within the molecule. The stabilization energy and charge delocalization of the 7B3M5D were performed by NBO analysis. This article assesses that the title compound act as a potential inhibitor of the PI3K/AKT inhibitor through in silico studies, like molecular docking, molecular dynamics (MD), ADMET prediction and also this molecule obeys Lipinski's rule of five. 7B3M5D was docked effectively in the active site of PI3K/AKT inhibitor.

SUBMITTER: Govindammal M

PROVIDER: S-EPMC8056428 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.

Project description:Background:Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs although its clinical use is limited by the severe cardiotoxicity. Apoptosis and defective autophagy are believed to contribute to DOX-induced cardiotoxicity. Here we explored the effect of curcumin (Cur) on DOX-induced cardiac injury and the mechanism involved with a focus on oxidative stress, autophagy and pyroptosis. Methods:Kunming mice were challenged with DOX (3 mg·kg-1, i.p. every other day) with cohorts of mice receiving Cur at 50, 100, 200 and 400 mg·kg-1 via gavage daily. Serum levels of cardiac enzymes, such as aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and heart homogenate oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Echocardiographic and cardiac contraction were examined. Apoptosis, pyroptosis, autophagy and Akt/mTOR-signalling proteins were detected using western blot or electron microscopy. Cardiac contractile properties were assessed including peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-PS, and time-to-90% relengthening (TR90). Superoxide levels were evaluated using DHE staining. GFP-LC3 was conducted to measure autophagosomes. Results:Our study showed that Cur protected against cardiotoxicity manifested by a significant decrease in serum myocardial enzymes and improvement of anti-oxidative capacity. Cur inhibited autophagy and offered overt benefit for cardiomyocyte survive against DOX-induced toxicity. Cur attenuated DOX-induced cardiomyocyte pyroptosis as evidenced by NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and interleukin-18 levels. DOX impaired cardiac function (reduced fractional shortening, ejection fraction, increased plasma cTnI level and TR90, decreased PS and ± dL/dt), the effects of which were overtly reconciled by 100 mg·kg-1 but not 50 mg·kg-1 Cur. H9c2 cells exposure to DOX displayed increased intracellular reactive oxygen species (ROS) and autophagy, the effects of which were nullified by Cur. Autophagy activator rapamycin cancelled off Cur-induced protective effects. Conclusions:Our finding suggested that Cur rescued against DOX-induced cardiac injury probably through regulation of autophagy and pyroptosis in a mTOR-dependent manner.

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Exploring the molecular structure, vibrational spectroscopic, quantum chemical calculation and molecular docking studies of curcumin: A potential PI3K/AKT uptake inhibitor.

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