Permeability data of organosulfur garlic compounds estimated by immobilized artificial membrane chromatography. Correlation across several biological barriers.

DANIELA RAMIREZ; FEDERICI, FERNANDA; ALTAMIRANO, JORGELINA CECILIA; ALEJANDRA B. CAMARGO; JUAN LUCO

Frontiers in Chemistry

Frontiers

Lugar: Connectitut; Año: 2021

Among healthy vegetables, those of the Allium genus stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur ompounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of said compounds once consumed, it is necessary to previously evaluate 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 (QSAR). 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 (QSRR) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds understudy on the 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´s ability to assess several ADME parameters for the OSCs understudy obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace, and preADMET web tool. The human gastrointestinal absorption (HIA), blood-brain barrier (BBB) permeation and skin permeability were investigated through QSAR modeling, using several chemometrics approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k?(IAM), which provides evidence for the great potential of the IAM phases in the development of QSAR models.