In Silico Toxicity and Efficacy Prediction of a Combination Drug, Namely, “Losartan Potassium and Hydrochlorothiazide”
Keywords:
Hypertension, Losartan Potassium, Hydrochlorothiazide, Molecular Docking, In-silico assessment, Toxicity, Computer-aided-drug-designingAbstract
Hypertension, the silent killer is one of the biggest public health concerns. Losartan is the second prescribed anti-hypertensive generic in terms of unit. Here molecular docking approach has been utilized to predict the efficacy and toxicity profile of ‘Losartan Potassium and Hydrochlorothiazide’ therapy. Docking is inquiring about an appropriate binding site for a ligand that suits energetically and linearly to the protein binding site. Firstly, the ligand was searched in PubChem. Canonical SMILE form was inputted in Protox for toxicity prediction. Swiss Target Prediction was used to find out the target proteins associated with efficacy and
toxicity. Proteins are responsible for desired and the undesired effect was downloaded from Protein Data Bank. Undesired ligand complexed was removed by PyMOL Protein and ligand may have unfavourable bond strength, bond length and torsion angle interfering with docking protocol. So Protein and ligand had undergone energy minimization by Swiss PDB
Viewer. Lastly, docking of Ligand, namely Losartan and Proteins, namely Endothelin receptor, PPAR gamma and Tyrosine Kinase ABL by PyRx was performed. Discovery Studio was used for visualization of the docking complex. Hydrochlorothiazide is predicted safe as it had shown no toxicity profile in Protox. The three proteins showed a very good vina binding
affinity with the ligand. It implies that Losartan causes both desired and undesired effect by binding with the proteins. Proteins responsible for immunotoxicity can form a conventional hydrogen bond, van der Waals interaction, Pi sigma, Pi alkyl and unfavourable donor-donor interaction with Losartan resulting in immunotoxicity and undesired effect. There is no common protein found for Losartan and Hydrochlorothiazide. So there is no chance of interaction for toxicity as well as efficacy. More study should be carried out to acknowledge the drug safer.
How to cite this article: Tanjin R, Roy MS, Debnath T et al. In Silico Toxicity and Efficacy Prediction of a Combination Drug, Namely, “Losartan Potassium and Hydrochlorothiazide”. Int J Adv Res Pharm Edu 2020; 2(2): 6-15.
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