# Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin
## 1 Introduction  
Bioavailability describes the properties of a drug which determine its absorption, distribution, metabolism, and elimination from an organism. One of the most important properties which determine bioavailability is lipophilicity, which describes the ability of a compound to cross the biological barrier. Often, with increased lipophilicity, the biological activity of a compound increases due to better permeability through biological membranes and a higher concentration of the compound inside the cell. However, too high lipophilicity may reduce the absorption of the compound due to its absorption in biological membranes [1; 2; 3; 4]. A measure of lipophilicity is the partition coefficient between non-polar and polar phases defined as P or logP. The precursor of the determination of the P coefficient was [PERSON], who designated the concentration of a compound in a composite mixture with two phases. As a non-polar and polar phase he used n-octanol and water, respectively. The method named \"shake-flask\" is laborious, time-consuming, and low-precision. For this reason, liquid chromatographic methods are most popular, namely,thin-layer chromatography in a normal phase system (NP-TLC) and its variant, thin-layer chromatography in a reversed phase system (RP-TLC). Thin-layer chromatography methods have many advantages compared with the \"shake-flask\" method. The most important is possibility of determined the lipophilicity of many compounds in the same time, low time-consuming, high-precisions and high reproducibility [5; 6; 7; 8; 9; 10]. Lipophilicity is connected to other parameters, like hydrophobicity (\(\varphi_{0}\)), permeability by Caco-2 membrane, skin, blood-brain barrier (BB), and penetration to the central nervous system (CNS). The design of a new compound is often supported by computational methods which determine the lipophilicity and permeability parameters using in silico methods [11; 12]. However, most programs determining the logP parameter calculate lipophilicity using atomic methods which do not include every structural parameter, such as the spatial arrangement of atoms or the position of a heterocyclic atom in a ring. In the literature, many examples of compounds described for which the theoretical lipophilicity is very different from the experimental one. The obtained theoretical value could eliminate the compounds from further research. For this reason, determining the correlation between experimental and theoretical parameters is still an important problem [13; 14; 15; 16; 17]. In the past few decades, the isolation of compounds from plant material has attracted considerable attention due to pharmacologically active compounds using in natural medicine. In many cases, natural compounds have moderate biological activity and bioavailability [18; 19; 20; 21]. One of the first compounds isolated in pure form from plant material was betulin (Figure 1). Betulin belongs to a pentacyclic triterpene alcohol with a lupane skeleton. The chemical structure of betulin contains four six-member rings and one five-member ring. Moreover, they have an isopropyllene group at the C19 position and two hydroxyl groups at the C3 and C28 positions. The compound is characterized by a broad spectrum of biological activity, like anticancer, antibacterial, antiviral, antifungal, hepatoprotective, and anti-inflammatory properties. The used of betulin in treatment is limited due to its low water solubility [22; 23; 24; 25; 26; 27; 28]. Chemical modifications of its structure allow new semisynthetic compounds to be obtained which have better biological properties. The replacement of one or two hydroxyl groups by an ester, amide, or carbamate group influences the activity and solubility in water of the obtained derivatives [29; 30]. An interesting trend observed in chemical synthesis is the introduction of heterocyclic moieties.