Organosulfur compounds permeability across several biological barriers employing immobilized artificial membrane chromatography

DANIELA RAMIREZ; JUAN LUCO; ALEJANDRA B. CAMARGO

Nanchang

Simposio; 5th International Symposium on Phytochemicals in Medicine and Food; 2021

Among healthy vegetables, those of the Allium genus stand out because of their numeroushealth-promoting properties, mainly attributed to organosulfur compounds (OSCs). To ensuretheir bioefficacy it is necessary to evaluate organosulfur compounds ADME (absorption,distribution, metabolism, and excretion) profile. In this sense, in-silico methods serve toprovide primary information on drugs´ bioavailability mechanisms. In the present study weemployed an Immobilized Artificial Membrane (IAM) HPLC column, and QuantitativeStructure-Activity Relationship (QSAR) modelling to assess several ADME parameters forthe OSCs understudy. In order to evaluate the ability of the IAM phase in assessinglipophilicity of the compounds under study, several quantitative structure-retentionrelationships (QSRR) were derived from exploring fundamental intermolecular interactionsthat govern the OSCs retention on the IAM phases. Based on these results and calculatedparameters corresponding to human gastrointestinal absorption (HIA), blood-brain barrier(BBB) permeation and skin permeability, different QSAR models were investigated usingchemometrics approaches. As expected, the hydrophobic factors prime the IAM-retention ofthese compounds. However, the molecular flexibility, and specific polar interactionsexpressed by several electronic descriptors (relative negative charge, RNCG, and Mullikenelectronegativity) were also involved. On the other hand, the ADME properties under studywere strongly dependent on hydrophobic factors as expressed by log k?(IAM). IAM phaseproved to be a suitable approach to assess membrane permeability of the target organosulfurcompounds.