Ester Groups as Carriers of Antivirally Active Tricyclic Analogue of Acyclovir in Prodrugs Designing: Synthesis, Lipophilicity - Comparative Statistical Study of the Chromatographic and Theoretical Methods, Validation of the HPLC Method

Title:Ester Groups as Carriers of Antivirally Active Tricyclic Analogue of Acyclovir in Prodrugs Designing: Synthesis, Lipophilicity - Comparative Statistical Study of the Chromatographic and Theoretical Methods, Validation of the HPLC Method

Volume: 17 Issue: 7

Author(s): Monika A. Lesniewska, Tomasz Ostrowski, Joanna Zeidler and Izabela Muszalska

Affiliation:

Keywords: HPLC, lipophilicity, tricyclic analogues of acyclovir.

Abstract: Knowledge of the lipophilicity of candidate compounds for prodrugs may predict their predetermined course/effect in the body. Acyclovir (ACV) belongs to a class of drugs with low bioavailability. Its tricyclic analogues, the derivatives of 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine (TACV) exhibit similar antiviral activities and are more lipophilic as compared with acyclovir itself. In the search for new antiviral prodrugs 6-(4- methoxyphenyl) tricyclic compound (6-(4-MeOPh)-TACV) was modified by esterification of a hydroxyl group in the aliphatic chain. Selected esters (acetyl, isobutyryl, pivaloyl, ethoxycarbonyl and nicotinoyl) were synthesized and their lipophilicity was determined by the HPLC-RP method. The study compared the log kw calculated from the linear and quadratic equations and proved the correctness of the application of the linear relationship log k as a function of the concentration of ACN in the mobile phase (30-60%). Statistical analyses of the comparative values of log k_w and clogP were carried out using computational methods. It was proved that the AC logP algorithm can be useful for the analysis of these compounds, which can have a statistically justified application in the assessment of the quantitative structure– activity relationship (QSAR). The lipophilicity determined by the HPLC method appears as follows: 6-(4-MeOPh)-TACV < Ac- < Nic- < Etc- < iBut- < Piv- (log kw = 0.65-2.26). Finally, the HPLC-RP method was developed and validated for simultaneous determination of synthesized esters.

Cite this article as:

Lesniewska A. Monika, Ostrowski Tomasz, Zeidler Joanna and Muszalska Izabela, Ester Groups as Carriers of Antivirally Active Tricyclic Analogue of Acyclovir in Prodrugs Designing: Synthesis, Lipophilicity - Comparative Statistical Study of the Chromatographic and Theoretical Methods, Validation of the HPLC Method, Combinatorial Chemistry & High Throughput Screening 2014; 17 (7) . https://dx.doi.org/10.2174/1386207317666140526100532