Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study
Objectives: The Human Telomerase enzyme has become a drug target in the treatment of cancers and age-related disorders. This study aims to identify potential natural inhibitors of the Human Telomerase from compounds derived from edible African plants. Materials and methods: A library of 1,126 natura...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844021018454 |
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| author | Adekunle Babajide Rowaiye Yoroshi Joana Teca Mendes Samson Ayodeji Olofinsae John Breakthrough Oche Oluwakemi Hannah Oladipo Okiemute Ajiroghene Okpalefe Joyce Oloaigbe Ogidigo |
| author_facet | Adekunle Babajide Rowaiye Yoroshi Joana Teca Mendes Samson Ayodeji Olofinsae John Breakthrough Oche Oluwakemi Hannah Oladipo Okiemute Ajiroghene Okpalefe Joyce Oloaigbe Ogidigo |
| author_sort | Adekunle Babajide Rowaiye |
| collection | DOAJ |
| description | Objectives: The Human Telomerase enzyme has become a drug target in the treatment of cancers and age-related disorders. This study aims to identify potential natural inhibitors of the Human Telomerase from compounds derived from edible African plants. Materials and methods: A library of 1,126 natural compounds was molecularly docked against the Telomerase Reverse Transcriptase (PDB ID: 5ugw), the catalytic subunit of the target protein. Curcumin, a known Telomerase inhibitor was used as the standard. The front-runner compounds were screened for bioavailability, pharmacokinetic properties, and bioactivity using the SWISSADME, PKCSM, and Molinspiration webservers respectively. The molecular dynamic simulation and analyses of the apo and holo proteins were performed by the Galaxy supercomputing webserver. Results: The results of the molecular docking and virtual screening reveal Augustamine and Camptothecin as lead compounds. Augustamine has better drug-likeness and pharmacokinetic properties while Camptothecin showed better bioactivity and stronger binding affinity (-8.2 kcal/mol) with the target. The holo structure formed by Camptothecin showed greater inhibitory activity against the target with a total RMSF of 169.853, B-Factor of 20.164, and 108 anti-correlating residues. Conclusion: Though they both act at the same binding site, Camptothecin induces greater Telomerase inhibition and better molecular stability than the standard, Curcumin. Further tests are required to investigate the inhibitory activities of the lead compounds. |
| first_indexed | 2024-12-17T21:30:07Z |
| format | Article |
| id | doaj.art-4d7a2b297c3b4e3a8528dd71dd7f0d75 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-17T21:30:07Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4d7a2b297c3b4e3a8528dd71dd7f0d752022-12-21T21:31:55ZengElsevierHeliyon2405-84402021-08-0178e07742Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational studyAdekunle Babajide Rowaiye0Yoroshi Joana Teca Mendes1Samson Ayodeji Olofinsae2John Breakthrough Oche3Oluwakemi Hannah Oladipo4Okiemute Ajiroghene Okpalefe5Joyce Oloaigbe Ogidigo6Department of Medical Biotechnology, National Biotechnology Development Agency, Abuja, NigeriaDepartment of Biochemistry, Nile University of Nigeria, Abuja, NigeriaDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria; Corresponding author.Department of Biochemistry, Federal University Gusau, Zamfara, NigeriaBioresources Development Centre, National Biotechnology Development Agency, Ilorin, NigeriaDepartment of Genetics, Genomics and Bioinformatics, National Biotechnology Development Agency, Abuja, NigeriaBioresources Development Centre, National Biotechnology Development Agency, Abuja, NigeriaObjectives: The Human Telomerase enzyme has become a drug target in the treatment of cancers and age-related disorders. This study aims to identify potential natural inhibitors of the Human Telomerase from compounds derived from edible African plants. Materials and methods: A library of 1,126 natural compounds was molecularly docked against the Telomerase Reverse Transcriptase (PDB ID: 5ugw), the catalytic subunit of the target protein. Curcumin, a known Telomerase inhibitor was used as the standard. The front-runner compounds were screened for bioavailability, pharmacokinetic properties, and bioactivity using the SWISSADME, PKCSM, and Molinspiration webservers respectively. The molecular dynamic simulation and analyses of the apo and holo proteins were performed by the Galaxy supercomputing webserver. Results: The results of the molecular docking and virtual screening reveal Augustamine and Camptothecin as lead compounds. Augustamine has better drug-likeness and pharmacokinetic properties while Camptothecin showed better bioactivity and stronger binding affinity (-8.2 kcal/mol) with the target. The holo structure formed by Camptothecin showed greater inhibitory activity against the target with a total RMSF of 169.853, B-Factor of 20.164, and 108 anti-correlating residues. Conclusion: Though they both act at the same binding site, Camptothecin induces greater Telomerase inhibition and better molecular stability than the standard, Curcumin. Further tests are required to investigate the inhibitory activities of the lead compounds.http://www.sciencedirect.com/science/article/pii/S2405844021018454TelomeraseMolecular dynamic simulationPharmacokineticAugustamineCamptothecin |
| spellingShingle | Adekunle Babajide Rowaiye Yoroshi Joana Teca Mendes Samson Ayodeji Olofinsae John Breakthrough Oche Oluwakemi Hannah Oladipo Okiemute Ajiroghene Okpalefe Joyce Oloaigbe Ogidigo Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study Heliyon Telomerase Molecular dynamic simulation Pharmacokinetic Augustamine Camptothecin |
| title | Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study |
| title_full | Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study |
| title_fullStr | Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study |
| title_full_unstemmed | Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study |
| title_short | Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study |
| title_sort | camptothecin shows better promise than curcumin in the inhibition of the human telomerase a computational study |
| topic | Telomerase Molecular dynamic simulation Pharmacokinetic Augustamine Camptothecin |
| url | http://www.sciencedirect.com/science/article/pii/S2405844021018454 |
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