Nair, Divya Gopalakrishnan and Narayanan, Sunilkumar Puthenpurackal and Chittalakkottu, Sadasivan (2015) Interactions of some commonly used drugs with human alpha-thrombin. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 33 (5). pp. 1008-1015. ISSN 0739-1102, 1538-0254
Full text not available from this repository. (Request a copy)Abstract
Adverse side effects of drugs are often caused by the interaction of drug molecules to targets other than the intended ones. In this study, we investigated the off-target interactions of some commercially available drugs with human alpha-thrombin. The drugs used in the study were selected from Super Drug Database based on the structural similarity to a known thrombin inhibitor argatroban. Interactions of these drugs with thrombin were initially checked by in silico docking studies and then confirmed by thrombin inhibition assay using a fluorescence microplate-based method. Results show that the three commonly used drugs piperacillin (anti-bacterial), azlocillin (anti-bacterial), and metolazone (anti-hypertensive and diuretic) have thrombin inhibitory activity almost similar to that of argatroban. The K-i values of piperacillin, azlocillin, and metolazone with thrombin are .55, .95, and .62 nM, respectively. The IC50 values of piperacillin, azlocillin, and metolazone with thrombin are 1.7, 2.9, and 1.92 nM, respectively. This thrombin inhibitory activity might be a reason for the observed side effects of these drugs related to blood coagulation and other thrombin activities. Furthermore, these compounds (drugs) may be used as anti-coagulants as such or with structural modifications.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CORONARY-OCCLUSION; BINDING; INHIBITORS; THROMBOLYSIS; PROTEINS; GEOMETRY; DATABASE; DOCKING; SYSTEM; drug side effects; argatroban; thrombin inhibition; docking; off-target interactions |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jul 2019 09:23 |
| Last Modified: | 18 Jul 2019 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5518 |
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