Calculation of the phenanthrene reactivity and pharmacodynamics in Dendrobium officinale
WENG Yueyue1, 2, LI Zhenyue1, 2, YU Deguan2, 3, ZENG Jingjie1, WU Shoubiao1, LIU Xiaoxiao1, WANG Chaojie2.
1.Department of Pharmacy, the Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou 325000, China; 2.School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; 3.Department of Pharmacy, Wenzhou People’s Hospital, Wenzhou 325000, China
WENG Yueyue,LI Zhenyue,YU Deguan, et al. Calculation of the phenanthrene reactivity and pharmacodynamics in Dendrobium officinale[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(9): 689-696.
Abstract：Objective: To investigate the structural characteristics, spectral properties, reactivity, and pharmacodynamic properties of phenanthrenes in Dendrobium officinale using density functional theory combined with ACD/Labs percepta platform. Methods: The structure and spectral properties of 12 phenanthrene compounds in Dendrobium officinale were calculated at the level of ωB97XD/6-311+G (d, p) in the density functional theory.The reactivity including molecular surface electrostatic potential, global and local reactivity descriptors were calculated. And then the pharmacodynamic parameters were predicted by ACD/labs percepta platform. Results:12 phenanthrenes had good solvent stability. The theoretical value of UV-Vis spectra agrees well with the experimental data. The reactivity order of 12 phenanthrene compounds is phenanthrene quinone > phenanthrene>dihydrophenanthrene. The reaction site of each compound was compared: compounds 1-8 (phenanthrene type), C9 and C10 had the highest reaction activity; compound 9 (phenquinone type) had the highest reaction activity on ketone group. Compounds 10, 11, 12 (dihydrophenanthrene type) had strong reactivity with C2 and C7 linked to the electron-donating group. Among the 12 compounds, -OH(O) was prone to electrophilic reaction.Pharmacodynamics analysis showed that all the 12 phenanthrenes were in line with Lipinski pharmacological principle, with good passive diffusion ability and strong plasma protein binding ability, and might have slight genotoxicity. Compounds 6, 7, 8 were moderately absorbed in the small intestine, which did not easily pen-etrate the blood-brain barrier and hardly had inhibitory effect on liver drug enzymes. Compounds 6, 7, 8, 9 and 12 had no cardiotoxicity. Conclusion: Theoretical investigation revealed the structure-activity relationship of phenanthrenes in Dendrobium officinale and elucidated their active sites, which provides theoretical support for subsequent structural modification and pharmacokinetic studies.
