Academic Journal
In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.
| Τίτλος: | In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment. |
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| Συγγραφείς: | Oyinloye BE; Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa.; Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria., Shamaki DE; Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa., Agbebi EA; Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; Department of Pharmacognosy and Natural Products, College of Pharmacy, Afe Babalola University, Ado-Ekiti 360001, Nigeria., Onikanni SA; Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan., Ubah CS; Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA 19121, USA., Aruleba RT; Department of Physiology, East Carolina University, Greenville, NC 27834, USA., Dao TNP; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.; Department of Traditional Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam., Owolabi OV; Medical Biochemistry Unit, College of Medicine and Health Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria., Idowu OT; Industrial Chemistry Unit, Department of Chemical Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti 360001, Nigeria., Mathenjwa-Goqo MS; Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa., Esan DT; Faculty of Nursing Sciences, College of Health Sciences, Bowen University, Iwo 232102, Nigeria., Ajiboye BO; Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Oye-Ekiti 371104, Nigeria., Omotuyi OI; Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.; Department of Pharmacology and Toxicology, College of Pharmacy, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria. |
| Πηγή: | Molecules (Basel, Switzerland) [Molecules] 2024 Apr 23; Vol. 29 (9). Date of Electronic Publication: 2024 Apr 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, c1995- |
| Ιατρικοί όροι (MeSH): | Azadirachta*/chemistry , Schistosomiasis*/drug therapy , Oxidoreductases Acting on CH-CH Group Donors*/antagonists & inhibitors , Oxidoreductases Acting on CH-CH Group Donors*/metabolism , Molecular Docking Simulation* , Dihydroorotate Dehydrogenase*, Phytochemicals/pharmacology ; Phytochemicals/chemistry ; Schistosoma mansoni/drug effects ; Schistosoma mansoni/enzymology ; NADH, NADPH Oxidoreductases/antagonists & inhibitors ; NADH, NADPH Oxidoreductases/metabolism ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Schistosomicides/pharmacology ; Schistosomicides/chemistry ; Schistosomicides/therapeutic use ; Multienzyme Complexes/antagonists & inhibitors ; Multienzyme Complexes/metabolism ; Praziquantel/pharmacology ; Praziquantel/chemistry ; Praziquantel/therapeutic use ; Animals ; Humans ; Molecular Dynamics Simulation ; Computer Simulation |
| Περίληψη: | The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug. |
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| Contributed Indexing: | Keywords: Azadirachta indica; dihydroorotate dehydrogenase; pharmacophore; schistosomiasis; simulation |
| Substance Nomenclature: | 0 (Dihydroorotate Dehydrogenase) EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors) 0 (Phytochemicals) EC 1.6.4.- (thioredoxin glutathione reductase) EC 1.6.- (NADH, NADPH Oxidoreductases) 0 (Plant Extracts) 0 (Schistosomicides) 0 (Multienzyme Complexes) 6490C9U457 (Praziquantel) |
| Entry Date(s): | Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240514 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11084920 |
| DOI: | 10.3390/molecules29091909 |
| PMID: | 38731401 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1420-3049 |
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| DOI: | 10.3390/molecules29091909 |