Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis DOI Creative Commons

Salim Bitrus Anyubaga,

Gideon Adamu Shallangwa, Adamu Uzairu

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 10(1), P. e23115 - e23115

Published: Dec. 3, 2023

The quest for a sound treatment on the vulnerable population suffering and dying as result of blood flukes, S. mansoni is increase because both Praziquantel Oxamniquine widely used Schistosomiasis over 51 years suffer resistance recurrence. Here-in, chemo-informatics techniques such QSAR modeling, pharmacokinetic, docking alongside MD simulation were harnessed in designing novel 7-keto- sempevirolsempevirol derivatives that are more competent against mansoni. Upon screening, compound 15, which appears to be model's acceptability space, emerges best with high predicted activity. 5 new analogues improved activity better than standard drug PZQ designed from 15 (template 15*) an account descriptors significance model robust validated parameters. Also their pharmacokinetic profiles indicates compounds have characteristics good drug. Furthermore, evaluation fulfilled ranges −113.121 −100.79 kcal/mol (moldock score), U1 being (least moldock score compared 15* (template) having value (−87.21 −83.37 kcal/mol). 100-ns Simulation U1-docked complex was run using Desmond 2019–4 package. nature steadiness within enzyme active site further confirmed by RMSD, RMSF, RoG H-bond assessment. Hence, we recommend targeting SmCB1 (6YI7) medicinal utilization.

Language: Английский

Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis DOI Creative Commons

Salim Bitrus Anyubaga,

Gideon Adamu Shallangwa, Adamu Uzairu

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 10(1), P. e23115 - e23115

Published: Dec. 3, 2023

The quest for a sound treatment on the vulnerable population suffering and dying as result of blood flukes, S. mansoni is increase because both Praziquantel Oxamniquine widely used Schistosomiasis over 51 years suffer resistance recurrence. Here-in, chemo-informatics techniques such QSAR modeling, pharmacokinetic, docking alongside MD simulation were harnessed in designing novel 7-keto- sempevirolsempevirol derivatives that are more competent against mansoni. Upon screening, compound 15, which appears to be model's acceptability space, emerges best with high predicted activity. 5 new analogues improved activity better than standard drug PZQ designed from 15 (template 15*) an account descriptors significance model robust validated parameters. Also their pharmacokinetic profiles indicates compounds have characteristics good drug. Furthermore, evaluation fulfilled ranges −113.121 −100.79 kcal/mol (moldock score), U1 being (least moldock score compared 15* (template) having value (−87.21 −83.37 kcal/mol). 100-ns Simulation U1-docked complex was run using Desmond 2019–4 package. nature steadiness within enzyme active site further confirmed by RMSD, RMSF, RoG H-bond assessment. Hence, we recommend targeting SmCB1 (6YI7) medicinal utilization.

Language: Английский

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