Table 3 Physiochemical properties of compounds BZ1 and BZ1-I
Parameter | BZ1 | BZ1-I | Remarks |
|---|---|---|---|
Molecular weight (MW) | 304.39 | 352.44 | Both compounds fall within the optimal MW range (<500 Da) for oral bioavailability. |
Polar surface area (PSA) (Ų) | 35.4 | 35.4 | Low PSA indicated favourable permeability across biological membranes. |
Fraction rotatable bonds (FRB) | 4 | 4 | Moderate flexibility; suitable for drug-likeness. |
Hydrogen bond donors (HBD) | 1 | 1 | Low HBD enhances membrane permeability. |
Hydrogen bond acceptors (HBA) | 3 | 2 | Fewer HBAs supported lipophilicity and target binding. |
Aromatic rings | 3 | 4 | Multiple aromatic rings may aid in target binding via π–π interactions. |
Fsp³ | 0.25 | 0.13 | Low Fsp³ may reduce solubility but increase target specificity. |
Predicted pKa | Basic: 8.1 | Basic: 8.1 | Basicity may influence interactions with the acidic environments in the parasitic lifecycle. |
cLogP | 4.7 | 6.0 | BZ1-I is more lipophilic, potentially enhanced passive permeability but risking poor solubility. |
cLogD at pH 7.4 | 3.9 | 5.2 | Higher cLogD of BZ1-I indicated stronger nonspecific binding to plasma proteins. |
gLogD at pH 7.4 | 5.0 | >5.3 | Excessive lipophilicity of BZ1-I could impair pharmacokinetics and lead to aggregation. |
Solubility (Sol 2.0/6.5 μg/mL) | >100/12.5–25 | 25–50/1.6–3.1 | BZ1 showed superior solubility compared to BZ1-I, especially at pH 6.5, relevant to parasitic environments. |
