Chromatographic and computational lipophilicity assessment of novel antibiofilm agents
Abstract
In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated
for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to
decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity
was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on
BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting
of acetonitrile and 20mmol/L ammonium-acetate solution in different ratios. Retention data
was used to derivatize the lipophilicity estimates logkw, S and u0: Computational substructurebased
and property-based methods were employed to calculate the logP, logD, milogP, AlogP,
XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing
hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly
evaluate the prediction ability... of each method. This test unambiguously recognized SðC18Þ, AlogP
and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound
denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL
PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development.
Keywords:
Antibiofilm agents / in silico / lipophilicity / RP-HPLC / Sum of Ranking DifferencesSource:
Journal of Liquid Chromatography & Related Technologies, 2020, 43, 15-16, 615-623Publisher:
- Taylor & Francis Inc.
Funding / projects:
DOI: 10.1080/10826076.2020.1777154
ISSN: 1082-6076
WoS: 000554670800001
Scopus: 2-s2.0-85087144122
Collections
Institution/Community
PharmacyTY - JOUR AU - Krmar, Jovana AU - Protić, Ana AU - Đajić, Nevena AU - Zečević, Mira AU - Otašević, Biljana PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4902 AB - In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting of acetonitrile and 20mmol/L ammonium-acetate solution in different ratios. Retention data was used to derivatize the lipophilicity estimates logkw, S and u0: Computational substructurebased and property-based methods were employed to calculate the logP, logD, milogP, AlogP, XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly evaluate the prediction ability of each method. This test unambiguously recognized SðC18Þ, AlogP and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development. PB - Taylor & Francis Inc. T2 - Journal of Liquid Chromatography & Related Technologies T1 - Chromatographic and computational lipophilicity assessment of novel antibiofilm agents VL - 43 IS - 15-16 SP - 615 EP - 623 DO - 10.1080/10826076.2020.1777154 ER -
@article{ author = "Krmar, Jovana and Protić, Ana and Đajić, Nevena and Zečević, Mira and Otašević, Biljana", year = "2020", abstract = "In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting of acetonitrile and 20mmol/L ammonium-acetate solution in different ratios. Retention data was used to derivatize the lipophilicity estimates logkw, S and u0: Computational substructurebased and property-based methods were employed to calculate the logP, logD, milogP, AlogP, XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly evaluate the prediction ability of each method. This test unambiguously recognized SðC18Þ, AlogP and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development.", publisher = "Taylor & Francis Inc.", journal = "Journal of Liquid Chromatography & Related Technologies", title = "Chromatographic and computational lipophilicity assessment of novel antibiofilm agents", volume = "43", number = "15-16", pages = "615-623", doi = "10.1080/10826076.2020.1777154" }
Krmar, J., Protić, A., Đajić, N., Zečević, M.,& Otašević, B.. (2020). Chromatographic and computational lipophilicity assessment of novel antibiofilm agents. in Journal of Liquid Chromatography & Related Technologies Taylor & Francis Inc.., 43(15-16), 615-623. https://doi.org/10.1080/10826076.2020.1777154
Krmar J, Protić A, Đajić N, Zečević M, Otašević B. Chromatographic and computational lipophilicity assessment of novel antibiofilm agents. in Journal of Liquid Chromatography & Related Technologies. 2020;43(15-16):615-623. doi:10.1080/10826076.2020.1777154 .
Krmar, Jovana, Protić, Ana, Đajić, Nevena, Zečević, Mira, Otašević, Biljana, "Chromatographic and computational lipophilicity assessment of novel antibiofilm agents" in Journal of Liquid Chromatography & Related Technologies, 43, no. 15-16 (2020):615-623, https://doi.org/10.1080/10826076.2020.1777154 . .