Investigation on the inclusion of diclofenac with β-cyclodextrin: a molecular modeling approach

Sahra, Khalil; Dinar, Karim; Seridi, Achour; Kadri, Mekki

doi:10.1007/s11224-014-0468-5

Cited by 19 publications

(15 citation statements)

References 41 publications

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“…The existence of the mentioned intramolecular N-H· · · O H-bond in DCL is utilized to modify the drug with, e.g., transition metals [18][19][20], cyclodextrin [21] or PEG [22], to increase its water solubility and oral bioavailability. Up to now, no research on the N-H· · · O dynamics at finite temperature was made.…”

Section: Introductionmentioning

confidence: 99%

Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

2017

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Diclofenac is the world known nonsteroidal antiinflammatory drug (NSAID) predicted before its syntesis on the basis of the model COX enzyme. Due to its specific structural properties the drug possesses high reactivity and outstanding tolerability. Among the key features defining the diclofenac structure is intramolecular N-H· · · O hydrogen bond confirmed during the X-ray analysis. In the present research we use static DFT calculations, the Quantum Theory of Atoms in Molecules and non-covalent interactions (NCI) index to confirm the additional intramolecular interactions, which influence the drug molecular structure. We focus on the structural stability of diclofenac as the result of the hydrogen bonds breaking/formation at finite temperature utilizing ab initio molecular dynamics simulations. The lifetime of different intramolecular hydrogen bonds is estimated. We perform also the comparative analysis of the structural stability of ibuprofen and ketoprofen molecules in the gas phase at 300 K with respect to diclofenac in terms of the NSAID inhibition activity. Due to the detailed description of diclofenac intramolecular interactions, possible drug modifications for its enhanced water solubility can be suggested.

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Section: Introductionmentioning

confidence: 99%

Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

2017

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“…17 This method has been applied in several earlier studies on inclusion complexes with cyclodextrins. [18][19][20][21][22][23][24][25][26][27] It allows to handle hydrogen bonds 28 and, as shown in ref. [18][19][20][21], predicts structural properties of such systems which are coherent with experimental results.…”

Section: Methods Of Calculationsmentioning

confidence: 99%

Quantum chemical study and isothermal titration calorimetry of β-cyclodextrin complexes with mianserin in aqueous solution

2017

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β-Cyclodextrin (β-CD) is studied as a carrier of the drug mianserin (MIA). β-CD with MIA adducts with 1 : 1 and 2 : 1 stoichiometry are investigated in vacuo and in water using quantum chemical methods: PM6 and B3LYP/6-31G(d,p). An effect of the dispersion correction GD2 and the basis set superposition error on the complexation energies is also evaluated. Additionally, the interaction between MIA hydrochloride and β-CD in aqueous solution at 298.15 K is examined experimentally by isothermal titration calorimetry. Interaction parameters, such as the binding constant, enthalpy, entropy and Gibbs free energy, are presented. Analysis of the obtained data led to the following conclusions: the interaction of MIA with β-CD is rather strong; there is no significant energetic difference between the 1 : 1 complexes of β-CD with S-MIA and R-MIA enantiomers; the 2 : 1 (β-CD : MIA) adduct is energetically more favorable than 1 : 1; the complex formation of MIA + β-CD is enthalpy and entropy driven.

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“…[14] Sahra et al [82] simulated host-guest interactions between diclofenac and β-CD using the semi-empirical PM6, PM3, and the quantum hybrid ONIOM (B3LYP/3-21 g: PM3 and B3LYP/3-21 g: PM6) approaches, to gain further insights into the non-covalent interaction in this system. Another molecular modeling study of lamotrigine/β-CD inclusion complex was performed using gAussiAn 03 W version 6.0 and hyperchem 7.51 packages, respectively, for quantum and molecular mechanics methods.…”

Section: Quantum Mechanicsmentioning

confidence: 99%

Computer‐aided drug design to explore cyclodextrin therapeutics and biomedical applications

Abdolmaleki

Ghasemi

2017

Chem Biol Drug Des

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Cyclodextrin (CD) is a subset of the macrocyclic structural class, which is an important class of small organic agents that are useful functional excipients. They have wide range application possibilities in different fields of sciences such as material preparation, medicine, analytical chemistry, and separation processes. They are used widely in pharmaceutical formulations and drug delivery for increasing the water solubility of low soluble drugs and drug candidates. Due to the ring structure, they behave differently than smaller molecules and may be capable of hitting new classes of targets. A macrocyclic molecule presents varied functionality and stereochemical complexity in a pre-organized conformation of the ring structure. This can result in high selectivity and affinity for protein targets while conserving enough bioavailability to arrive at intracellular locations. Regardless of these valuable features, and the verified success of several marketed macrocycle drugs isolated from natural compounds, this class has been little explored in drug development. This study describes some of the key features of the CDs therapeutic discovery. Also, the application of computational chemistry approaches such as QSAR/QSPR, molecular docking, and molecular/quantum mechanics for modeling of CD-drug system is reviewed briefly. K E Y W O R D Sbioavailability, computational, cyclodextrin, drug design, drug discovery, macrocyclic, therapeutic

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Investigation on the inclusion of diclofenac with β-cyclodextrin: a molecular modeling approach

Cited by 19 publications

References 41 publications

Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

Structural stability of diclofenac vs. inhibition activity from ab initio molecular dynamics simulations. Comparative study with ibuprofen and ketoprofen

Quantum chemical study and isothermal titration calorimetry of β-cyclodextrin complexes with mianserin in aqueous solution

Computer‐aided drug design to explore cyclodextrin therapeutics and biomedical applications

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