Inclusion Complexation of Praziquantel and -Cyclodextrin, Combined Molecular Mechanic and Monte Carlo Simulation

Abstract

Schistosomiasis is an infectious disease caused by parasitic worms. Large doses are necessary to achieve adequate concentrations at the destination due to low solubility of praziquantel. We use Monte Carlo simulations to generate structures of the water that will act as a solvent around praziquantel molecule with aim to study the formation of the solvation shells of the molecule after complexation into cyclodextrin. In this work it had shown an increased of the water number around praziquantel/ -cyclodextrin complexes in relation isolated praziquantel molecule. This increase of the water number is due to hydrophilic effect of the cyclodextrin molecule.

Investigation of Praziquantel/Cyclodextrin Inclusion Complexation by NMR and LC-HRMS/MS: Mechanism, Solubility, Chemical Stability, and Degradation Products

“…PZQ and β-CD complex formation has been long established; ,,− however, a comprehensive and detailed analysis of a such system is still missing. Due to limited PZQ water solubility, our initial NMR experiments were performed in DMSO- d 6 , enabling the preparation of highly concentrated samples, and consequently fast acquisition and well-defined NMR spectra.…”

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

“…[46] Today, hundreds of computational calculations describe drug-CD complexes reports. Table 1 classifies a number of present research studies in this field: molecular docking, [47][48][49] MD, [50][51][52][53] quantitative structure-activity/ property relationships (QSARs/QSPRs), [54][55][56] quantum mechanics (QM), [57][58][59] Monte Carlo (MC) simulations, [60][61][62] and machine learning.…”

“…β-CD and four derivatives of β-CD Luteolin [47] Molecular docking HP-β-CD and methylated β-CD Voriconazole [58] β-CD 4,4′-Dihydroxybiphenyl [59] β-CD 57 Guest molecules [50] Molecular dynamics (MD) β-and γ-CD Amphotericin B [51] α-, β-, and γ-CD Cumene hydroperoxide [52] α-and β-CD 1-Alkanols, substituted phenols, and substituted imidazoles [53] α-CD Benzene derivatives [54] Quantitative structure-activity/ property relationships (QSARs/QSPRs) β-CD Multiple compounds [55] β-CD 233 Molecules [56] β-CD Dopamine and epinephrine [57] Quantum mechanics (QM) α-CD Carboplatin, oxaliplatin, nedaplatin [58] β-CD Aflatoxin B1 [59] β-CD Praziquantel [60] Monte Carlo (MC) simulations β-CD and methylated β-CD Niobocene dichloride [61] α-CD Water [62] Sulfobutylether β-CD Diverse organic molecules [63] Machine learning…”

“…With MC methods, a complex system is able to be sampled in many random configurations, and all data can be useful to reproduce the full of the system. [60] However, MC simulation attributes by repeated random sampling act and records the consequences in casino-like conditions. The outcomes with low energies must be accumulated.…”

“…Water molecules were found to be useful in forming praziquantel/β-CD complexes due to the hydrophilic effect posed on the CD molecule. [60] MC simulations have also been used to study water molecules inside the hydrophobic cavity of α-CD. [62] The results showed that about five water molecules are present in the CD cavity; however, only 2.4 of these molecules on average interacts with α-CD by hydrogen bonds, which is fewer than the number interacting with the molecule outside the cavity.…”