Discovering L-type calcium channels inhibitors of antihypertensive drugs based on drug repositioning.
- Author:
Ying-xi LIANG
;
Yu-su HE
;
Lu-di JIANG
;
Qiao-xin YUE
;
Shuai CUI
;
Li BIN
;
Xiao-tong YE
;
Xiao-hua ZHANG
;
Yang-ling ZHANG
- Publication Type:Journal Article
- MeSH:
Animals;
Antihypertensive Agents;
chemistry;
pharmacology;
Calcium Channel Blockers;
chemistry;
pharmacology;
Calcium Channels, L-Type;
genetics;
metabolism;
Drug Repositioning;
methods;
Molecular Structure;
Myocardium;
metabolism;
Rabbits
- From:
China Journal of Chinese Materia Medica
2015;40(18):3650-3654
- CountryChina
- Language:Chinese
-
Abstract:
This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
