scholarly journals Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers

2021 ◽  
Vol 9 ◽  
Author(s):  
Daniela Andrea Ramirez ◽  
María Fernanda Federici ◽  
Jorgelina Cecilia Altamirano ◽  
Alejandra Beatriz Camargo ◽  
Juan María Luco

Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals’ use and provide preliminary information on drugs’ ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs’ bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure–activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k’ (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure–retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k’(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.

2019 ◽  
Vol 136 ◽  
pp. 104945 ◽  
Author(s):  
Cristina Alonso ◽  
Víctor Carrer ◽  
Sonia Espinosa ◽  
Miriam Zanuy ◽  
Mònica Córdoba ◽  
...  

2007 ◽  
Vol 26 (3) ◽  
pp. 317-332 ◽  
Author(s):  
Santiago Vilar ◽  
Elías Quezada ◽  
Carlos Alcaide ◽  
Francisco Orallo ◽  
Lourdes Santana ◽  
...  

2005 ◽  
Vol 11 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Chi Ho Yoon ◽  
Soo Jin Kim ◽  
Beom Soo Shin ◽  
Kang Choon Lee ◽  
Sun Dong Yoo

The chromatographic capacity factors (kIAM) of 23 structurally diverse drugs were measured by the immobilized artificial membrane (kIAM) phosphatidylcholine chromatography for the prediction of blood-brain barrier (BBB) penetration. The kIAM was determined using themobile phase consisting of acetonitrile:DPBS (20:80 v/v) and corrected for the molar volume of the solutes (kIAM/MWn). The correlation between kIAM/MWn and CNS penetration was highest when measured at pH 5.5 with the power function of n = 4. This in vitro predictionmethod was validated with 7 newly synthesized PDE-4 inhibitors. The relationship between in vivo plasma-to-brain concentration ratios and in vitro CNS penetration was excellent ( r= 0.959). The developed in vitro prediction method may be used as a rapid screening tool for BBB penetration of drugs with passive transport mechanism, with high success, low cost, and reproducibility.


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