# Assessment of Bioavailability Parameters of Mono- and Bistriazole Derivatives of Propynoylbetulin
## 5 Conclusions  
This research shows that triazole derivatives of betulin are characterized by high values of lipophilicity (logP\({}_{\text{TILC}}\)) which is in the range from 3.75 to 8.83. Mono- and bistriazoles have similar logP\({}_{\text{TILC}}\) values. The lowest values were obtained for compounds with a hydroxyl group as the triazole substituent (**7**, **9**, **15**, and **17**). This research shows that lipophilicity depends on the type of substituent at the triazole moiety. The introduction of a triazole ring influences the water solubility of the compound. Comparing the hydrophobicity index of propynoyl betulin and its triazole derivatives shows that triazole compounds have better solubility. Moreover, bistriazoles have slightly better water solubil  
Figure 5: The similarity analyses of ADME parameters and experimental lipophilicity for compounds **3–18**.  
ity than monotriazoles. The experimental lipophilicity was compared with the lipophilicity determined using computer programs. The milogP and XLOGP3 programs best reproduce the experimental lipophilicity.  
The bioavailability of compounds was determined using in silico-calculated Lipinski and Veber parameters. The analysis of parameters shows that monotriazoles **3-10** could be used as orally administered drugs while bistriazoles **11-18** have low absorption after oral administration. The molecular weight and topological polar surface could be used to determine lipophilicity, and the obtained logP\({}_{\text{calc}}\) better reproduces the experimental value than the theoretical logP.  
The last part of the study was the determination of in silico pharmacokinetic parameters responsible for the permeability of the gastrointestinal system, skin, and blood-brain barrier. The parameters determining the absorption from the gastrointestinal system (logPapp and HIA index) show that monotriazole derivatives **(3-10)** were characterized by better Caco-2 membrane penetration than bistriazoles **(11-18)**. Triazoles could be used as transdermal drugs because the logKp is lower than \(-2.5\). The tested compounds were poorly distributed in the central nervous system. The similarity analysis showed that the ADME parameters depend on the type of substituent in the triazole moiety. Mono- and bistriazoles have similar properties.  
The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app14051695/s1](https://www.mdpi.com/article/10.3390/app14051695/s1)]([https://www.mdpi.com/article/10.3390/app14051695/s1](https://www.mdpi.com/article/10.3390/app14051695/s1)), Table S1: The theoretical value of lipophilicity of compounds **3-18**. Table S2: The similarity parameter (ED) for the theoretical and experimental lipophilicity for compounds **3-18**.  
Conceptualization, methodology, and writing--original draft preparation, M.K.-T.; methodology, A.S. and K.S.; validation and formal analysis, E.B. and E.C.; writing--review and editing, P.O. All authors have read and agreed to the published version of the manuscript.  
This research was funded by the Medical University of Silesia, grant number BNW-1-013/N/3/F.  
Not applicable.  
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.  
The authors declare no conflicts of interest.