betadex and benzyl-isothiocyanate

The formation of host-guest complex between benzyl isothiocyanate (BITC) and β-cyclodextrin (β-CD) was studied using dispersion-corrected density functional theory calculations. The complexation process was monitored using molecular docking simulations, natural bond orbital (NBO) technique, nuclear magnetic resonance (

Topics: beta-Cyclodextrins; Density Functional Theory; Isothiocyanates; Models, Molecular; Molecular Structure

Methyl-β-cyclodextrin (MβCD) is an effective agent for the removal of plasma membrane cholesterol. In this study, we investigated the modulating effects of MβCD on the antiproliferation induced by benzyl isothiocyanate (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that MβCD dose-dependently increased the cholesterol level in the medium, possibly through its removal from the plasma membrane of human colorectal cancer cells. The pretreatment with a non-toxic concentration (2.5 mM) of MβCD significantly enhanced the BITC-induced cytotoxicity and apoptosis induction, which was counteracted by the cholesterol supplementation. Although BITC activated the phosphoinositide 3-kinase (PI3K)/Akt pathway, MβCD dose-dependently inhibited the phosphorylation level of Akt. On the contrary, the treatment of MβCD enhanced the phosphorylation of mitogen activated protein kinases, but did not potentiate their BITC-induced phosphorylation. These results suggested that MβCD might potentiate the BITC-induced anti-cancer by cholesterol depletion and thus inhibition of the PI3K/Akt-dependent survival pathway. Abbreviations: CDs: cyclodextrins; MβCD: methyl-β-cyclodextrin; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; PI3K: phosphoinositide 3-kinase; PDK1: phosphoinositide-dependent kinase-1; MAPK: mitogen activated protein kinase; ERK1/2: extracellular signal-regulated kinase1/2; JNK: c-Jun N-terminal kinase; PI: propidium iodide; FBS: fatal bovine serum; TLC: thin-layer chromatography; PBS(-): phosphate-buffered saline without calcium and magnesium; MEK: MAPK/ERK kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PIP3: phosphatidylinositol-3,4,5-trisphosphate.

Topics: Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Cell Line, Tumor; Cell Proliferation; Cholesterol; Colorectal Neoplasms; Culture Media; Dose-Response Relationship, Drug; Drug Synergism; Humans; Isothiocyanates; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt

The use of methodical and innovative sonication method has been explored for the fabrication of inclusion complex of Benzyl Isothiocyanate, a potential anticancer and -antimicrobial agent. The advancement involved investigation of inclusion behaviour, characterisation and an in-depth study of thermal and UV stability of Benzyl Isothiocyanate with cyclodextrins; β-CD and hp-β-CD. The sonication driven encompassment in cyclodextrins helped to overcome the hindrance of low solubility and high volatility. Investigations of physical and thermodynamic parameters using UV-visible spectroscopy, FTIR, XRD, TGA etc confirmed stability of inclusion complexes. Both β-CD and hp-β-CD based inclusion complexes retained the antimicrobial property of the free Benzyl Isothiocyanate, indicating their potential utility as antimicrobial agents. Haematological safety and cellular uptake data gives direction to in-depth analysis for its exploitation of anti-tumour activity.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Drug Carriers; Drug Stability; Isothiocyanates; Models, Molecular; Molecular Conformation; Solubility; Thermodynamics; Ultrasonic Waves; Volatilization

The inclusion complex of benzyl isothiocyanate (BITC), extracted from papaya seed with β-cyclodextrin (β-CD), was prepared. Different analytical techniques, such as Fourier transform infrared spectroscopy, thermal analysis, X-ray diffractometry, particle size distribution analysis and (1)H Nuclear magnetic resonance analysis, were used to investigate the characterization of the inclusion complex (BITC-β-CD). All these approaches indicated that the inclusion complex was capable of being formed. The inclusion complex exhibited different spectroscopic and thermodynamic features and properties from BITC, and we deduced the possible inclusion modes for BITC-β-CD. The calculated apparent stability constant of the BITC-β-CD was 600.8l/mol, and the aqueous solubility of BITC was indistinctively improved by phase solubility studies. The results illustrated that β-CD was a proper excipient for increasing the stability and controlled release of BITC. Thus, β-CD complexation technology would be a promising approach, in expanding the application of BITC as a food antibacterial agent.

Topics: beta-Cyclodextrins; Carica; Drug Stability; Excipients; Isothiocyanates; Magnetic Resonance Spectroscopy; Particle Size; Seeds; Solubility; Spectroscopy, Fourier Transform Infrared; Thermodynamics