Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis
The quest for a sound treatment on the vulnerable population suffering and dying as a result of the blood flukes, S. mansoni is on the increase because both Praziquantel and Oxamniquine widely used for the treatment of Schistosomiasis for over 51 years suffer resistance and recurrence. Here-in, chem...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023103239 |
| _version_ | 1797337079612440576 |
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| author | Salim Bitrus Anyubaga Gideon Adamu Shallangwa Adamu Uzairu Stephen Eyije Abechi |
| author_facet | Salim Bitrus Anyubaga Gideon Adamu Shallangwa Adamu Uzairu Stephen Eyije Abechi |
| author_sort | Salim Bitrus Anyubaga |
| collection | DOAJ |
| description | The quest for a sound treatment on the vulnerable population suffering and dying as a result of the blood flukes, S. mansoni is on the increase because both Praziquantel and Oxamniquine widely used for the treatment of Schistosomiasis for over 51 years suffer resistance and recurrence. Here-in, chemo-informatics techniques such as QSAR modeling, pharmacokinetic, docking alongside MD simulation were harnessed in designing novel 7-keto- sempevirolsempevirol derivatives that are more competent against S. mansoni. Upon QSAR screening, compound 15, which appears to be in the model's acceptability space, emerges the best with a high predicted activity. 5 new analogues with improved activity against Schistosomiasis better than the standard drug PZQ were designed from compound 15 (template 15*) on an account of the descriptors significance from the model with robust and validated parameters. Also their pharmacokinetic profiles indicates that the designed compounds have the characteristics of a good drug. Furthermore, docking evaluation fulfilled ranges from −113.121 to −100.79 kcal/mol (moldock score), with compound U1 being the best (least moldock score of −113.121 compared to PZQ and 15* (template) having a moldock score value of (−87.21 and −83.37 kcal/mol). 100-ns MD Simulation on the U1-docked complex was run using Desmond 2019–4 package. The nature and steadiness of U1 compound within the enzyme active site was further confirmed by RMSD, RMSF, RoG and H-bond assessment. Hence, we recommend compound U1 targeting the SmCB1 enzyme (6YI7) for Schistosomiasis treatment and for further medicinal evaluation and utilization. |
| first_indexed | 2024-03-08T09:04:14Z |
| format | Article |
| id | doaj.art-313c4bcf7c0044458986b4d73ec3c9c6 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:04:14Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-313c4bcf7c0044458986b4d73ec3c9c62024-02-01T06:30:48ZengElsevierHeliyon2405-84402024-01-01101e23115Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of SchistosomiasisSalim Bitrus Anyubaga0Gideon Adamu Shallangwa1Adamu Uzairu2Stephen Eyije Abechi3Corresponding author.; Department of Chemistry Ahmadu Bello University, P.M.B. 1044, Zaria, NigeriaDepartment of Chemistry Ahmadu Bello University, P.M.B. 1044, Zaria, NigeriaDepartment of Chemistry Ahmadu Bello University, P.M.B. 1044, Zaria, NigeriaDepartment of Chemistry Ahmadu Bello University, P.M.B. 1044, Zaria, NigeriaThe quest for a sound treatment on the vulnerable population suffering and dying as a result of the blood flukes, S. mansoni is on the increase because both Praziquantel and Oxamniquine widely used for the treatment of Schistosomiasis for over 51 years suffer resistance and recurrence. Here-in, chemo-informatics techniques such as QSAR modeling, pharmacokinetic, docking alongside MD simulation were harnessed in designing novel 7-keto- sempevirolsempevirol derivatives that are more competent against S. mansoni. Upon QSAR screening, compound 15, which appears to be in the model's acceptability space, emerges the best with a high predicted activity. 5 new analogues with improved activity against Schistosomiasis better than the standard drug PZQ were designed from compound 15 (template 15*) on an account of the descriptors significance from the model with robust and validated parameters. Also their pharmacokinetic profiles indicates that the designed compounds have the characteristics of a good drug. Furthermore, docking evaluation fulfilled ranges from −113.121 to −100.79 kcal/mol (moldock score), with compound U1 being the best (least moldock score of −113.121 compared to PZQ and 15* (template) having a moldock score value of (−87.21 and −83.37 kcal/mol). 100-ns MD Simulation on the U1-docked complex was run using Desmond 2019–4 package. The nature and steadiness of U1 compound within the enzyme active site was further confirmed by RMSD, RMSF, RoG and H-bond assessment. Hence, we recommend compound U1 targeting the SmCB1 enzyme (6YI7) for Schistosomiasis treatment and for further medicinal evaluation and utilization.http://www.sciencedirect.com/science/article/pii/S2405844023103239SchistosomiasisBlood flukesQSARDocking-simulationPharmacokineticsMD simulation |
| spellingShingle | Salim Bitrus Anyubaga Gideon Adamu Shallangwa Adamu Uzairu Stephen Eyije Abechi Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis Heliyon Schistosomiasis Blood flukes QSAR Docking-simulation Pharmacokinetics MD simulation |
| title | Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis |
| title_full | Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis |
| title_fullStr | Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis |
| title_full_unstemmed | Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis |
| title_short | Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis |
| title_sort | chemo informatics applications in the design of novel 7 keto sempervirol derivatives as smcb1 inhibitors with potential for treatment of schistosomiasis |
| topic | Schistosomiasis Blood flukes QSAR Docking-simulation Pharmacokinetics MD simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023103239 |
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