title: Quantitative structure-retention relationship of curcumin and its analogues.
abstract: The natural product curcumin is widely used in Asian countries for the treatment of several diseases. However, the clinical potential of curcumins remains limited due to their relatively poor bioavailability and no experimental data about their lipophilicity for bioavailability prediction. To evaluate the retention and lipophilicity of curcumin and its 31 newly synthesized analogues, they were subjected to 3D quantitative structure-retention relationship studies by RP-HPLC. Superior than the classical four-variant quantitative structure-retention relationship model (conventional r(2) =0.734), the 3D comparative molecular similarity index analysis model with combined steric, electrostatic, and H-bond donor fields, resulted in a robust structure-retention correlation (cross-validated q(2) =0.613 and r(2) =0.979). The statistical analyses indicate that the electrostatic and H-bond donor fields have a primary influence on the chromatographic retention of analytes. The predictive power and robustness of the derived comparative molecular similarity index analysis model was further confirmed by the test-set validation (q(2) =0.702, r(2) =0.905, and the slope K=1.016) and Y-randomization examination. Statistically significant and physically meaningful 3D-quantitative structure-retention relationship provided better insight into understanding the retention behaviors of curcumin and its analogues, and their separation mechanism in a given RP-HPLC system.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Xue-Hua
authors.initials: XH
authors.lastname: Zheng
authors.forename: Yong-Xian
authors.initials: YX
authors.lastname: Shao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Bu
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001688:Biological Products; D003474:Curcumin