Abstract
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.
Highlights
The current guidelines recommend diets rich in fruits and vegetables as an important factor in reducing the risk of developing chronic diseases (Yu et al, 2018)
Evidence has shown that organosulfur compounds (OSCs) present in different garlic matrices interfere against inflammation, oxidative stress, obesogenic effects, and mitochondrial dysfunction (Quesada et al, 2020) by multiple actions, such as modifying signaling pathways that trigger chronic diseases
If we focus on the bioactive efficacy, we must first ensure that the phytochemical compounds manage to reach the target sites within the body where they will exert their biological effect, so it is necessary to previously evaluate in vivo the ADME profile of the said compounds (Rein et al, 2013)
Summary
The current guidelines recommend diets rich in fruits and vegetables as an important factor in reducing the risk of developing chronic diseases (Yu et al, 2018). To estimate cellular permeability there have been several absorption models that are proposed, including cell-based models, using the human colorectal adenocarcinoma (Caco-2) cell line and the Madin-Darby Canine Kidney (MDCK) cell line and tissuebased models, such as in situ rat intestinal perfusion or the Ussing chamber system employing rat or human intestinal tissues (Berben et al, 2018). Computational approaches (in silico) serve to provide primary information on drugs’ bioavailability mechanisms (Yen et al, 2005) In this context, alternative methods, such as chromatographic ones, employing immobilized artificial membrane (IAM) chromatographic columns, have been widely recognized as a valuable tool to model processes in the biophase since the components of both chromatographic and biological systems are comparable. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches
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