Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-10, Vol.27 (19), p.6504
• Main Authors: Sharapova, Angelica, Ol’khovich, Marina, Blokhina, Svetlana, Perlovich, German L
• Format: Article
• Language: English
• Subjects: Biological activity; biphasic system; Buffer solutions; Chemical partition; Chemical properties; Coefficients; Dependence; Drug discovery; Equilibrium; Evaluation; Fluconazole; Fungicides; Gastrointestinal system; Gastrointestinal tract; Hybrids; Lipophilic; Lipophilicity; Mechanical properties; new antimycotic compounds; Octanol; Organic compounds; partition coefficient; Pharmacokinetics; Physicochemical properties; Solubility; Solvents; Thermal properties; Thermodynamics; transfer
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27196504

The important physicochemical properties of three novel bioactive hybrid compounds with different groups (-CH3, -F and -Cl) were studied, including kinetic and thermodynamic solubility in pharmaceutically relevant solvents (buffer solutions and 1-octanol) as well as partition coefficient in system 1-octanol/buffer pH 7.4. The aqueous solubility of these chemicals is poor and ranged from 0.67 × 10−4 to 1.98 × 10−3 mol·L−1. The compounds studied are more soluble in the buffer pH 2.0, simulating the gastrointestinal tract environment (by an order of magnitude) than in the buffer pH 7.4 modelling plasma of blood. The solubility in 1-octanol is significantly higher; that is because of the specific interactions of the compounds with the solvent. The prediction solubility behaviour of the hybrid compounds using Hansen’s three-parameter approach showed acceptable results. The experimental solubility of potential drugs was successfully correlated by means of two commonly known equations: modified Apelblat and van’t Hoff. The temperature dependencies of partition coefficients of new hybrids in the model system 1-octanol/buffer pH 7.4 as a surrogate lipophilicity were measured by the shake flask method. It was found that compounds demonstrated a lipophilic nature and have optimal values of partition coefficients for oral absorption. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than fluconazole. In addition, the thermodynamic aspects of dissolution and partition processes have been examined. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than the reference drug.