# Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin
## 4 Discussion  
The use of new synthesised compounds in therapy depends on their biological activity and bioavailability. One of the most important properties of compounds is their lipophilicity which determines drug transport across the biological barrier. The determination of lipophilicity offers the opportunity to assess the availability and toxicity of a potential drug [1]. The propynoyl derivatives of betulin **1** and **2** are characterized by high lipophilicity which is equal to 6.68 and 9.20, respectively. Compounds **3-18** create two groups, the first of which includes the monotirazole derivatives of **1** and the second consists of the bistriazole derivatives of **2**. In the group of monotirazole compounds **3-10**, the lowest logPTLC value is shown by derivative 7 with the deoxy-\(\beta\)-D-glucopyranosyl substituent at the triazole ring. Derivatives of the benzyl group **(3-5)** exhibit comparable lipophilicity which is in the range from 7.09 to 7.24. The introduction of the phenylotinethyl group at the triazole ring, compound **6**, increases lipophilicity. Comparing the logPTLC value of compounds **1** and **8-10** shows that the introduction of a substituent with oxygen and nitrogen atoms decreases lipophilicity. The transformation of 3,28-dipropynoylbetulin **2** to bistriazole derivatives **11-18** decreases lipophilicity. Similar to the first group, in the group of bistriazole derivatives, the lowest value of lipophilicity is shown by compound **15** with the deoxy-\(\beta\)-D-glucopyranosyl substituent. In these groups of compounds **(11-18)**, similar correlations were observed as for **3-10**. Comparing the lipophilicity of mono- and bistriazole compounds containing the same substituents at the triazole ring, bistriazole derivatives had higher log PTLC values. The exceptions were the compounds with a \(\beta\)-D-glucopyranosyl substituent (7 and **15**) and a hydroxypropyl substituent (**9** and **17**), of which derivatives with one triazole ring (7 and **9**) had higher lipophilicity. The hydrophobicity index describes the water solubility of a compound; if the \(\varphi_{0}\) value is lower, then water solubility is better [59]. Comparing the \(\varphi_{0}\) value of triazole derivatives **3-18** and compounds **1-2** shows that the introduction of a triazole ring increases water solubility. The hydrophobicity index is in the range from 73.11 to 86.86 and from 59.69 to 86.29 for mono- **3-10** and bistriazoles **11-18**, respectively. The results show that mono- and bistriazole derivatives have comparable solubility in water. Before determining the experimental lipophilicity, it is necessary to synthesize and purify the tested compound. The experimental method is not useful during the computer design of new active compounds. For this reason, the experimental lipophilicity is replaced by theoretical methods which use a different algorithm [60; 61; 62]. The calculated lipophilicity for triazole compounds **3-18** was determined using theoretical methods used in software that is available online [52; 53]. The obtained values were in the range from 1.17 to 13.42 (Table 3). For all programs, the theoretical lipophilicity depends on the type of substituent at the triazole ring. A relationship was observed, namely, that monotirazoles **3-10** have lower lipophilicity than bistriazoles **11-18**. The exceptions are compounds **7** and **15** containing the deoxy-\(\beta\)-D-glucopyranosyl substituent. Bistriazole derivative **15** has lower lipophilicity due to the larger number of hydroxyl groups which reduces the logP parameter. Comparing the experimental and theoretical lipophilicity shows that logP values obtained using the AClogP and ALOGPs programs are lower than the experimental one (Figure 3). For other programs, the calculated lipophilicity is higher than the experimental logPTLC. Due to the fact that different programs use different calculating algorithms, an important aspect of the research is to determine the correlation between the experimental and theoretical lipophilicity (Table 5).