Naslov
Study of lipophilicity and membrane partition of 4-hydroxycoumarins by HPLC and PCA

Autori
Ilijaš, Marina ; Malnar, Ivica ; Gabelica Marković, Vesna ; Stepanić, Višnja

Izvornik
Journal of pharmaceutical and biomedical analysis (0731-7085) 76 (2013); 104-111

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
4-hydroxycoumarins; HPLC; CHI; CHI IAM; structure-retention reletaionship

Sažetak
Physicochemical properties provide reliable guidance in optimization of pharmacological efficiency and ADME profile of small chemical compounds. Their high-throughput determination is regularly based on application of HPLC techniques. In this study CHI and CHI IAM of 32 4-hydroxycoumarin analogs were measured by HPLC with methanol gradient at pHs 2.8 and 7.0. Results were analyzed by PCA in terms of computed descriptors in order to identify space for optimization of their phospholipids affinity and lipophilicity for which predictive software failed to produce reliable estimations. The chromatographic behavior of studied 4-hydroxycoumarins was typical of acidic compounds. The CHI2.8, CHI7.0, CHI IAM2.8 and CHI IAM7.0 values were all considerably cross-correlated in accordance with their prevailing lipophilic character. Structure–retention relationship (SRR) analysis furthermore revealed that H-bond accepting capacity and dipolar interactions with methanol generally shorten their retention times. However, deviations from the linear trends were noticed for R3/R5-substituted derivatives able to form intramolecular contacts with the 4-O(H) group and characterized by more uniform electron density at 2-O and 4-O atoms and quite different acidity/H-bond donating capacity than the rest of derivatives. Thus, CHI and CHI IAM determinations and SRR analysis fast and efficiently pointed to ways of modifying biological activities of 4-hydroxycoumarins.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA