دورية أكاديمية
Ligand-protein interactions of plant-isolated (9z,12z)-octadeca-9,12-dienoic acid with Β-ketoacyl-Acp synthase (KasA) in potential anti-tubercular drug designing.
| العنوان: | Ligand-protein interactions of plant-isolated (9z,12z)-octadeca-9,12-dienoic acid with Β-ketoacyl-Acp synthase (KasA) in potential anti-tubercular drug designing. |
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| المؤلفون: | Mtewa AG; Chemistry Section, Department of Applied Studies, Institute of Technology, Malawi University of Science and Technology, Malawi.; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda., Bvunzawabaya JT; Department of Biomedical Sciences, Kamuzu University of Health Sciences, Blantyre, Malawi.; Africa Centre of Excellence in Public Health and Herbal Medicine (ACEPHEM), Kamuzu University of Health Sciences, Malawi., Ngwira KJ; School of Chemistry, Institute of Molecular Science, University of Witwatersrand, South Africa., Lampiao F; Department of Biomedical Sciences, Kamuzu University of Health Sciences, Blantyre, Malawi.; Africa Centre of Excellence in Public Health and Herbal Medicine (ACEPHEM), Kamuzu University of Health Sciences, Malawi., Maghembe R; Biotechnology Section, Centre for Chemistry and Chemical Engineering, Lund University, Lund, Sweden.; Marian University College, Department of Biological and Marine Sciences, Bagamoyo, Tanzania., Okella H; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda., Weisheit A; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda., Tolo CU; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda., Ogwang PE; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda., Sesaazi DC; Pharmbiotechnology and Traditional Medicine Centre (PHARMBIOTRAC), Mbarara University of Science and Technology, Mbarara, Uganda. |
| المصدر: | Scientific African [Sci Afr] 2021 Jul; Vol. 12, pp. e00824. Date of Electronic Publication: 2021 Jun 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V. on behalf of African Institute of Mathematical Sciences Next Einstein Initiative Country of Publication: Netherlands NLM ID: 101771789 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2468-2276 (Electronic) Linking ISSN: 24682276 NLM ISO Abbreviation: Sci Afr Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V. on behalf of African Institute of Mathematical Sciences Next Einstein Initiative, [2018]- |
| مستخلص: | Mycobacterium tuberculosis remains one of the world's contributors to mortality. With the emergence of SARS-CoV-2 coinfections, patients with TB are predisposed to being more heavily weighed down by COVID-19 disease and its opportunistic coinfections. The severity of the disease coupled with drug resistance on the currently used drugs warrants for the search for alternative remedies from synthetic agents, semisynthetics and natural products that include plants. Africa is rich in plant diversity with a promise as sources of drug agents, one of which is Eichhornia crassipes . This work aimed at isolating a fatty acid and dock it to β-ketoacyl-ACP synthase for possible anti-TB drug development prospects using computational tools. (9z,12z)-Octadeca-9,12-dienoic acid was isolated from Eichhornia crassipes for the first time using chromatographic techniques and identified using 1D and 2D NMR spectroscopic methods ( 1 H NMR, COSY, HSQC, HMBC and 13 C NMR). The compound was then docked to β-ketoacyl-ACP synthase (KasA), an essential member of the b-ketoacyl synthases encoded in the M. tuberculosis genome in comparison with its co-crystallized ligand JSF-3285, also for the first time. (9z,12z)-Octadeca-9,12-dienoic acid interacted with only phenylalanine239 and proline201 while JSF-3285 interacted with proline201, glutamine120, alanine119, leucine116, glutamine199, histadine345, phenylalanine239, glycine240 and glycine200. (9z,12z)-Octadeca-9,12-dienoic acid had a ligand efficiency of 0.24, compared to the co-crystallized ligand's 0.36. The compound was too flexible and elongated with -4.72 KCalmol -1 binding energy. Despite some unfavourable physico-chemical properties, the compound still provides reliable interactions that only require logical structural modifications by the addition of polar regions amongst others to increase interactions and ligand efficiency, which can consequently stand to be a better potential drug lead. For the first time, plant-based (9z,12z)-Octadeca-9,12-dienoic acid isolated from Eichhornia crassipes was shown to interact fairly well with β-ketoacyl-ACP synthase and proved to be a potential starting material from which anti-tubercular drugs can be designed. Competing Interests: The authors declare no conflict of interests. (© 2021 The Authors.) |
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| فهرسة مساهمة: | Keywords: Computational chemistry; Drug design; Drug development; Drug-protein interactions; KasA inhibitor; Ligand efficiency; M. tuberculosis; Malawi; Medicinal Chemistry; β-ketoacyl-ACP synthase |
| تواريخ الأحداث: | Date Created: 20230522 Latest Revision: 20230523 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10190923 |
| DOI: | 10.1016/j.sciaf.2021.e00824 |
| PMID: | 37215382 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2468-2276 |
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| DOI: | 10.1016/j.sciaf.2021.e00824 |