Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV
Abstract The belief that we could always stay ahead of the pathogens was forced upon scientists in the whole world by antimicrobial resistance. According to several reports, there are medications that are yet to be made public in the pipeline and there are little motivations to design novel antimicr...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-96410-y |
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| author | Abel Kolawole Oyebamiji Sunday A. Akintelu Samson Olusegun Afolabi Emmanuel T. Akintayo Cecilia O. Akintayo Oluwakemi Ebenezer |
| author_facet | Abel Kolawole Oyebamiji Sunday A. Akintelu Samson Olusegun Afolabi Emmanuel T. Akintayo Cecilia O. Akintayo Oluwakemi Ebenezer |
| author_sort | Abel Kolawole Oyebamiji |
| collection | DOAJ |
| description | Abstract The belief that we could always stay ahead of the pathogens was forced upon scientists in the whole world by antimicrobial resistance. According to several reports, there are medications that are yet to be made public in the pipeline and there are little motivations to design novel antimicrobials to combat the worldwide drug resistance issues. Presently, the desire to design and develop efficient novel anti-bacterial agents is very high by researchers; thus, this study focuses on identifying the interactions between the studied ligands and Proplasmepsin IV, as well as examining the relationship between the calculated descriptors and binding affinities. This work shows successful prediction of the reacting and inhibiting efficiency of ten (10) cyclic tetra-peptides using insilico method. The optimization of the studied compound revealed the proficiency of methyl (3S,9S,12S)-12-(1,3-dioxoisoindolin-2-yl)-9-(2-(methylthio)ethyl)-5,8,11-trioxo-4,7,10-triaza-1(1,3)-benzenacyclotridecaphane-3-carboxylate (F5) and 2-((3S,9S,12S)-12-(1,3-dioxoisoindolin-2-yl)-3-(methoxycarbonyl)-5,8,11-trioxo-4,7,10-triaza-1(1,3)-benzenacyclotridecaphane-9-yl)acetic acid (F7) to react more than the remaining molecules in term of HOMO and LUMO energies. In comparison, compound F9 demonstrated a higher inhibitory activity than the reference drug, Chloroquine, based on binding affinity. Molecular dynamics simulations over a 100 ns period further explored the binding affinity between F9 and the reference drug. The results showed that the reference drug (− 21.91 ± 1.16 kcal/mol) had a slightly stronger binding affinity than the F9_complex (− 13.85 ± 0.72 kcal/mol). Additionally, pharmacokinetic studies for F9 were compared with those of the reference compound and presented accordingly. |
| format | Article |
| id | doaj-art-5fe6d8d0546c47878e080d20fb646bbd |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-5fe6d8d0546c47878e080d20fb646bbd2025-08-20T03:13:55ZengNature PortfolioScientific Reports2045-23222025-04-0115112410.1038/s41598-025-96410-yComputer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IVAbel Kolawole Oyebamiji0Sunday A. Akintelu1Samson Olusegun Afolabi2Emmanuel T. Akintayo3Cecilia O. Akintayo4Oluwakemi Ebenezer5Department of Industrial Chemistry, University of IlesaDepartment of Industrial Chemistry, University of IlesaLaboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO UniversityDepartment of Chemistry, Ekiti State UniversityDepartment of Chemistry, Federal UniversityDepartment of Physics, University of AlbertaAbstract The belief that we could always stay ahead of the pathogens was forced upon scientists in the whole world by antimicrobial resistance. According to several reports, there are medications that are yet to be made public in the pipeline and there are little motivations to design novel antimicrobials to combat the worldwide drug resistance issues. Presently, the desire to design and develop efficient novel anti-bacterial agents is very high by researchers; thus, this study focuses on identifying the interactions between the studied ligands and Proplasmepsin IV, as well as examining the relationship between the calculated descriptors and binding affinities. This work shows successful prediction of the reacting and inhibiting efficiency of ten (10) cyclic tetra-peptides using insilico method. The optimization of the studied compound revealed the proficiency of methyl (3S,9S,12S)-12-(1,3-dioxoisoindolin-2-yl)-9-(2-(methylthio)ethyl)-5,8,11-trioxo-4,7,10-triaza-1(1,3)-benzenacyclotridecaphane-3-carboxylate (F5) and 2-((3S,9S,12S)-12-(1,3-dioxoisoindolin-2-yl)-3-(methoxycarbonyl)-5,8,11-trioxo-4,7,10-triaza-1(1,3)-benzenacyclotridecaphane-9-yl)acetic acid (F7) to react more than the remaining molecules in term of HOMO and LUMO energies. In comparison, compound F9 demonstrated a higher inhibitory activity than the reference drug, Chloroquine, based on binding affinity. Molecular dynamics simulations over a 100 ns period further explored the binding affinity between F9 and the reference drug. The results showed that the reference drug (− 21.91 ± 1.16 kcal/mol) had a slightly stronger binding affinity than the F9_complex (− 13.85 ± 0.72 kcal/mol). Additionally, pharmacokinetic studies for F9 were compared with those of the reference compound and presented accordingly.https://doi.org/10.1038/s41598-025-96410-yPeptidesProplasmepsinInhibitorsInsilicoMalaria, molecular docking, molecular dynamics simulations134-Oxadiazole derivatives |
| spellingShingle | Abel Kolawole Oyebamiji Sunday A. Akintelu Samson Olusegun Afolabi Emmanuel T. Akintayo Cecilia O. Akintayo Oluwakemi Ebenezer Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV Scientific Reports Peptides Proplasmepsin Inhibitors Insilico Malaria, molecular docking, molecular dynamics simulations 134-Oxadiazole derivatives |
| title | Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV |
| title_full | Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV |
| title_fullStr | Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV |
| title_full_unstemmed | Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV |
| title_short | Computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of Proplasmepsin IV |
| title_sort | computer aided study on cyclic tetrapeptide based ligands as potential inhibitors of proplasmepsin iv |
| topic | Peptides Proplasmepsin Inhibitors Insilico Malaria, molecular docking, molecular dynamics simulations 134-Oxadiazole derivatives |
| url | https://doi.org/10.1038/s41598-025-96410-y |
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