UNS Conference Portal, The 1st International Conference on Science, Mathematics, Environment and Education 2017

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A New Candidate of Calcium Channel Blocker In Silico from Tectona grandis for Treatment of Gestational Hypertension
Yuliana Heri Suselo, Asma Azizah, Muthmainah Muthmainah, Dono Indarto

Last modified: 2017-07-24


Background: Gestational Hypertension is one of the three main causes of maternal mortality in Indonesia. Nifedipine which blocked the Cav1.2 calcium channel has frequently been used to treat gestational hypertension. However the prevalence of gestational hypertension is still high (27.1 %) and the efficacy of nifedipine has not been established. Indonesian herbal plants have potential to be developed as natural drugs. This study was to identify Indonesian herbal plants that could inhibit the calcium channel in silico.

Methods: This was a bioinformatics study with molecular docking approach. Three-dimensional structure of human calcium channel Cav1.2 was determined by modelling with rabbit calcium channel (access code: 5GJW) as template and using SWISS MODEL software. Nifedipine was used as a standard ligand and obtained from ZINC database with the access code ZINC19594578. Active compounds of Indonesian herbal plants were registered in HerbalDB database and their molecular structure was obtained from PubChem. Binding affinity of ligand-calcium channel complexes were assesed using AutoDock Vina 1.1.2 and visualization of molecular conformation used Chimera 1.10 and PyMol 1.3 software. The Lipinsky’s rules of five were used to determine active compounds which full filled drug criteria.

Results: The model human calcium channel had 72.35% sequence identity with rabbit Cav1.1. Nifedipine bound to the model human calcium channel with -2.1 kcal/mol binding affinity and had binding sites at Gln1060, Phe1129, Ser1132, and Ile1173 residues. A lower binding affinity was observed in obtusifolin 2-glucoside (-2.2 kcal/mol). This compound had similar binding sites as nifedipin. In addition, obtusifolin 2-glucoside met the Lipinsky criteria and the molecule conformation was similar with nifedipine. From the HerbalDB database, obtusifolin 2-glucoside was found in Tectona grandis.

Conclusions: Obtusifolin 2-glucoside becomes computationally a potensial candidate of calcium channel blocker. In vitro assays should be performed to evaluate the antagonist effect of obtusifolin 2-glucoside on calcium channel blocker Cav1.2.