Lipophilicity assessement in drug discovery: Experimental and theoretical methods applied to xanthone derivatives

Álvaro Santos; José Xavier Soares; Sara Cravo; Maria E Tiritan; Salette Reis; Carlos Afonso; Carla Fernandes; Madalena M M Pinto

doi:10.1016/j.jchromb.2017.10.018

Lipophilicity assessement in drug discovery: Experimental and theoretical methods applied to xanthone derivatives

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1:1072:182-192. doi: 10.1016/j.jchromb.2017.10.018. Epub 2017 Nov 10.

Authors

Álvaro Santos¹, José Xavier Soares², Sara Cravo³, Maria E Tiritan⁴, Salette Reis⁵, Carlos Afonso⁶, Carla Fernandes⁷, Madalena M M Pinto³

Affiliations

¹ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
² LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
³ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR), Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208, Porto, Matosinhos, Portugal.
⁴ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR), Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208, Porto, Matosinhos, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), Rua Central de Gandra, 1317, 4585-116, Gandra PRD, Portugal.
⁵ UCBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
⁶ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR), Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208, Porto, Matosinhos, Portugal. Electronic address: cafonso@ff.up.pt.
⁷ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal; Interdisciplinary Center of Marine and Environmental Investigation (CIIMAR), Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208, Porto, Matosinhos, Portugal. Electronic address: cfernandes@ff.up.pt.

PMID: 29175698
DOI: 10.1016/j.jchromb.2017.10.018

Abstract

For the last several years, searching of new xanthone derivatives (XDs) with potential pharmacological activities has remained one of the main areas of interest of our group. The optimization of biological activity and drug-like properties of hits and leads is crucial at early stage of the drug discovery pipeline. Lipophilicity is one of the most important drug-like properties having a great impact in both pharmacokinetics and pharmacodynamics processes. In this work, we describe the lipophilicity of a small library of bioactive XDs, previously synthesized by our group, using different methods: computational, vortex-assisted liquid-liquid microextraction coupled with high-performance liquid chromatography (VALLME-HPLC), reversed-phase high-performance thin layer chromatography (RP-HPTLC), reversed-phase high-performance liquid chromatography (RP-HPLC), and biomembrane model by the partition between micelles and aqueous phase. The different results obtained by the used methods were compared and discussed. The methodologies and data gathered in this study will expand the investigation of lipophilicity of XDs, an important class of compounds in medicinal chemistry.

Keywords: Biomembrane model; Lipophilicity; RP-HPLC; RP-HPTLC; VALLME-HPLC; Xanthone derivatives.

MeSH terms

Chromatography, High Pressure Liquid / methods
Chromatography, Reverse-Phase / methods
Drug Discovery / methods*
Hydrophobic and Hydrophilic Interactions
Xanthones / analysis*
Xanthones / chemistry*

Substances

Xanthones