دورية أكاديمية
Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery.
| العنوان: | Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery. |
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| المؤلفون: | Noh MAA; Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia., Fazalul Rahiman SS; Discipline of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia., A Wahab H; Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia., Mohd Gazzali A; Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia. |
| المصدر: | Journal of basic and clinical physiology and pharmacology [J Basic Clin Physiol Pharmacol] 2021 Jun 25; Vol. 32 (4), pp. 715-722. Date of Electronic Publication: 2021 Jun 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Walter de Gruyter Country of Publication: Germany NLM ID: 9101750 Publication Model: Electronic Cited Medium: Internet ISSN: 2191-0286 (Electronic) Linking ISSN: 07926855 NLM ISO Abbreviation: J Basic Clin Physiol Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jun. 2011- : Berlin : Walter de Gruyter Original Publication: London, England : Freund Pub. House, c1990- |
| مواضيع طبية MeSH: | Drug Discovery*, Antitubercular Agents/pharmacology ; Folic Acid ; Ligands ; Molecular Docking Simulation ; Pharmaceutical Preparations |
| مستخلص: | Objectives: Tuberculosis (TB) remains a public health concern due to the emergence and evolution of multidrug-resistant strains. To overcome this issue, reinforcing the effectiveness of first line antituberculosis agents using targeted drug delivery approach is an option. Glyceraldehyde-3-Phosphate Dehydrogenase (GADPH), a common virulence factor found in the pathogenic microorganisms has recently been discovered on the cell-surface of Mycobacterium tuberculosis , allowing it to be used as a drug target for TB. This study aims to discover active small molecule(s) that target GAPDH and eventually enhance the delivery of antituberculosis drugs. Methods: Ten ligands with reported in vitro and/or in vivo activities against GAPDH were evaluated for their binding interactions through molecular docking studies using AutoDock 4.2 program. The ligand with the best binding energy was then modified to produce 10 derivatives, which were redocked against GAPDH using previous protocols. BIOVIA Discovery Studio Visualizer 2019 was used to explore the ligand-receptor interactions between the derivatives and GAPDH. Results: Among the 10 ligands, curcumin, koningic acid and folic acid showed the best binding energies. Further analysis on the docking of two folic acid derivatives, F7 (γ-{[tert-butyl-N-(6-aminohexyl)]carbamate}folic acid) and F8 (folic acid N-hydroxysuccinimide ester) showed that the addition of a bulky substituent at the carboxyl group of the glutamic acid subcomponent resulted in improved binding energy. Conclusions: Folic acid and the two derivatives F7 and F8 have huge potentials to be developed as targeting agents against the GAPDH receptor. Further study is currently on-going to evaluate the effectiveness of these molecules in vitro . (© 2021 Walter de Gruyter GmbH, Berlin/Boston.) |
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| فهرسة مساهمة: | Keywords: Autodock; GAPDH; antituberculosis; drug delivery; folic acid; glyceraldehyde-3-phosphate dehydrogenase |
| المشرفين على المادة: | 0 (Antitubercular Agents) 0 (Ligands) 0 (Pharmaceutical Preparations) 935E97BOY8 (Folic Acid) |
| تواريخ الأحداث: | Date Created: 20210702 Date Completed: 20220214 Latest Revision: 20220214 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1515/jbcpp-2020-0435 |
| PMID: | 34214294 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2191-0286 |
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| DOI: | 10.1515/jbcpp-2020-0435 |