Structural modeling and identification of imperatorin as novel L-type calcium channel blocker.
L-type calcium channel (LTCC) blockers are used as cardiac antiarrhythmics or antihypertensives. In our previous research, we have reported a furanocoumarin, imperatorin, which exhibited potent vasodilatory effects. The possible mechanism might involve with inhibition against LTCC. In order to further investigate the pharmacologic mechanism of imperatorin for interaction with LTCC, the homology modeling of LTCC was performed using MODELLER 9.9 program with potassium channels as templates. The binding mode of imperatorin to LTCC was further investigated by molecular docking. Molecular docking results indicated that imperatorin occupied the same binding site as verapamil and hydrogen bond interaction played important role in blocker-channel binding. Docking studies provided useful information to understand the action mechanism of imperatorin. The results described here will be helpful in the development of novel potential LTCC blockers.
College of Medicine, Xi'an Jiaotong University, Xi' an, Shaanxi Province, 710061, P.R. China. zhj8623@mail.xjtu.edu.cn.
Wen
W
Lu
Tao
T
Zhang
Pengfei
P
Li
Fang
F
Wang
Xiaoyan
X
Pan
Chen
C
Wang
Zhigang
Z
Hu
Jie
J
Zhang
D000595:Amino Acid Sequence; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D011564:Furocoumarins / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D017385:Sequence Homology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011564:Furocoumarins; C031534:imperatorin