Molecular modifications of ibuprofen using Insilico modeling system (original) (raw)
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Journal of Crystal Growth, 2017
, which was generated from ibuprofen molecule by molecular simulation. The predicted crystal structures of ibuprofen with space group P2 1 /c has the lowest total energy and the largest density, which is nearly indistinguishable with experimental result. In addition, the XRD patterns for predicted crystal structure are highly consistent with recrystallization from solvent of ibuprofen. That indicates that the simulation can accurately predict the crystal structure of ibuprofen from the molecule. Furthermore, based on this crystal structure, we predicted the crystal habit in vacuum using the attachment energy (AE) method and considered solvent effects in a systematic way using the modified attachment energy (MAE) model. The simulation can accurately construct a complete process from molecule to crystal structure to morphology prediction. Experimentally, we observed crystal morphologies in four different polarity solvents compounds (ethanol, acetonitrile, ethyl acetate, and toluene). We found that the aspect ratio decreases of crystal habits in this ibuprofen system were found to vary with increasing solvent relative polarity. Besides, the modified crystal morphologies are in good agreement with the observed experimental morphologies. Finally, this work may guide computer-aided design of the desirable crystal morphology.
Molecules
A novel derivative of ibuprofen and salicylaldehyde N′-(4-hydroxybenzylidene)-2-(4-isobutylphenyl) propane hydrazide (HL) was synthesized, followed by its complexation with Cu, Ni, Co, Gd, and Sm. The compounds obtained were characterized by 1HNMR, mass spectrometry, UV-Vis spectroscopy, FT-IR spectroscopy, thermal analysis (DTA and TGA), conductivity measurements, and magnetic susceptibility measurements. The results indicate that the complexes formed were [Cu(L)(H2O)]Cl·2H2O, [Ni(L)2], [Co(L)2]·H2O, [Gd(L)2(H2O)2](NO3)·2H2O and [Sm(L)2(H2O)2](NO3)·2H2O. The surface characteristics of the produced compounds were evaluated by DFT calculations using the MOE environment. The docking was performed against the COX2 targeting protein (PDB code: 5IKT Homo sapiens). The binding energies were −7.52, −9.41, −9.51, −8.09, −10.04, and −8.05 kcal/mol for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, which suggests the enhancement of anti-inflammatory behaviors compared with the bin...
Molecules
Inflammation is a complex reaction involving cellular and molecular components and an unspecific response to a specific aggression. The use of scientific and technological innovations as a research tool combining multidisciplinary knowledge in informatics, biotechnology, chemistry and biology are essential for optimizing time and reducing costs in the drug design. Thus, the integration of these in silico techniques makes it possible to search for new anti-inflammatory drugs with better pharmacokinetic and toxicological profiles compared to commercially used drugs. This in silico study evaluated the anti-inflammatory potential of two benzoylpropionic acid derivatives (MBPA and DHBPA) using molecular docking and their thermodynamic profiles by molecular dynamics, in addition to predicting oral bioavailability, bioactivity and toxicity. In accordance to our predictions the derivatives proposed here had the potential capacity for COX-2 inhibition in the human and mice enzyme, due to con...
Synthesis of Ibuprofen Derivatives with Improved Antibacterial Activity
Asian Journal of Chemistry, 2015
Ibuprofen (NSAIDs), a member of propionic acid derivatives (2-arylpropionic acids) was first time introduced in 1969 as a superior alternative of aspirin 1. Having excellent pharmaceutical properties and better tolerating power, it is extensively used to relieve non-rheumatic inflammation, pain, acute arthritis, fever and primary dysmenorrehea 2. Repeated administrations are inevitable in most cases to achieve good therapeutic effects. Gastrointestinal (GI) ulceration and hemorrhage are very common side effects due to long-term oral administration but very fewer than aspirin 2. These side effects result from the direct contact attributed to the amalgamation of local irritation produced by the free carboxylic group in the molecular structure of ibuprofen due to inhibition of the cyclooxygenase (COX) in the gastrointestinal tract 3. Consequently, the development of bioreversible derivatives i.e. prodrugs is the need of time to decrease the toxicity induced by NSAIDs. Accorging to Bundgaard, prodrug is a compound that has ability to undergo biotransformation prior to exhibiting its pharmacological properties 4. A prodrugs normally comprise
Linear models for prediction of ibuprofen crystal morphology based on hydrogen bonding propensities
Fluid Phase Equilibria, 2009
Solvents have a significant impact on the final crystal form of organic solids during solution crystallization. The use of polarity scales such as Hildebrand solubility parameter and dielectric constant for solvent selection often proves too generalized and do not provide enough insights into the solvent-solute intermolecular interactions directly affecting crystal growth and morphology. This paper addresses the challenging task of selecting an appropriate single component solvent property index that most accurately and sufficiently characterizes crystal morphology. Cooling crystallization experiments were carried out in a wide range of solvents using ibuprofen as a model pharmaceutical compound. Subsequently, optical microscope images were used for quantitative characterization of morphology. Linear models that correlate ibuprofen crystal morphology with pure solvent properties were developed. Our results show that, in general, there is a negative linear correlation between crystal aspect ratio (morphology) and a given solvent index. Some correlations revealed significant deviations which were explained with the help of infrared spectroscopic measurements. The "acceptance number" was identified as an index that significantly captures the ibuprofen-solvent hydrogen bonding intermolecular interactions. Predictions, using model based on acceptance number, were found to compare very well with experimentally determined aspect ratio data from the open literature. Finally, based on insights gained from this work, a flowchart which serves as a useful solvent selection guideline for crystallization of ibuprofen is proposed.
American Journal of Advanced Drug Delivery
Prodrug is a substance which after administration is metabolized into a pharmacologically active drug. Actually prodrug has least medicinal value in in-vitro/in-vivo but after biotransformation by metabolism in invivo it releases the active medicament. A drug is a substance which is a chemical entity, has definite structural skeleton, obtained by natural or synthetic or semisynthetic source, which can fit on bioreceptor platform having controlling capacity to control over the biochemical malfunction. Every drug is xenobiotic because it is coming from outer source (xeno) and active in biological unit (biotic). Prodrug is the precursor of drug which is made by derivatization of the same to enhance the bioavailability by pharmacokinetics, lipid solubility by partition coefficient and increase the physicochemical and biochemical parameters by pharmacodynamics. Ibuprofen, Diclofenac and Paracetamol have been taken as NSAID (Non-Steroidal Anti Inflammatory Drug) and three prodrugs have been synthesized by reacting with acid chloride of ibuprofen and diclofenac with paracetamol to get prodrug of ester linkage and acid chloride of ibuprofen has been reacted with diclofenac to get prodrug of amide linkage. All three prodrugs showed different logP values and molecular weights according to the solubility parameters and electronegativity: logP profile: Prodrug-C>Prodrug-B>prodrug-A; molecular weight profile: Prodrug-C>Prodrug-B>prodrug-A.
Journal of Molecular Liquids, 2016
This paper highlights the benefits resulting from the application of double active pharmaceutical ingredient in ionic liquids as active pharmaceutical ingredients (APIs). Double active pharmaceutical ingredient benzalkonium ibuprofenate with anti-bacterial and anti-inflammatory roles, which offers high solubility, bio-availability, and biological activity. Structure and vibrational properties of NaIb, BaCl, and synthesized BaIb have been studied using Density Function Theory and are in good agreement with the experimental results of FTIR, UV-Visible, and NMR. The thermal and spectroscopic investigation using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS) revealed different phases of BaIb and disclosed the synthesized API is an excellent glass former. The glass transition temperature Tg = 194.14 K and fragility index m = 68.58 were estimated and compared with other members of the profen's family by Vogel-Fulcher-Tamman (VFT) equation. Finally, the in vitro and in vivo biological activities of the synthesized drug BaIb were done along with the parent drugs NaIb and BaCl as a control to ensure the double active effect.