In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates
Abstract Backgrond In silico studies are essential techniques in the modern medicinal chemistry. QSAR modeling and molecular docking are important techniques in both drug discovery and development and have been successfully deployed in the field of medicinal chemistry for the discovery, design, and...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-05-01
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| Series: | Bulletin of the National Research Centre |
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| Online Access: | http://link.springer.com/article/10.1186/s42269-020-00333-9 |
| _version_ | 1818289518379270144 |
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| author | Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu |
| author_facet | Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu |
| author_sort | Aliyu Wappah Mahmud |
| collection | DOAJ |
| description | Abstract Backgrond In silico studies are essential techniques in the modern medicinal chemistry. QSAR modeling and molecular docking are important techniques in both drug discovery and development and have been successfully deployed in the field of medicinal chemistry for the discovery, design, and development of many drug candidates. These techniques were used in this work to come up with a model that relate 2,5-disubstituted furans with their antiplasmodium activities for the development of more active antimalarial drugs. Results Predictive and robust QSAR model was generated using Genetic Function Algorithm. The model was statistically validated to have internal and external squared correlation coefficient, R 2 of 0.982 and 0.735 respectively; predictive squared correlation coefficient, R 2 pred of 0.599; adjusted squared correlation coefficient, R adj of 0.974; and leave-one-out cross-validation coefficient, Q 2 cv of 0.966. It was found out that the antiplasmodium activities of 2,5-disubstituted furans relied on the parameters: GATS5c, minsCl RDF130m, RDF75p, and RDF115s descriptors. All the descriptors except minsCl influenced the antiplasmodium activities of the compounds negatively. That is, their increase decreases the activities of the furans and vice versa. The docking study revealed that most of the furans bind more tightly to Plasmodium falciparum lactate dehydrogenase (pfLDH) than chloroquine, but the enzyme may not be their major target. Conclusion Insight into the relationship between 2,5-disubstituted furans and their antiplasmodium activities has been revealed from the results of this work. Therefore, this could serve as a model for designing novel 2,5-disubstituted furans as potential antimalarial drugs with better activities. |
| first_indexed | 2024-12-13T02:13:31Z |
| format | Article |
| id | doaj.art-821162de8be8415494b7127debead7a0 |
| institution | Directory Open Access Journal |
| issn | 2522-8307 |
| language | English |
| last_indexed | 2024-12-13T02:13:31Z |
| publishDate | 2020-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Bulletin of the National Research Centre |
| spelling | doaj.art-821162de8be8415494b7127debead7a02022-12-22T00:02:58ZengSpringerOpenBulletin of the National Research Centre2522-83072020-05-0144111010.1186/s42269-020-00333-9In silico studies of 2,5-disubstituted furans as active antimalarial drug candidatesAliyu Wappah Mahmud0Gideon Adamu Shallangwa1Adamu Uzairu2Department of Applied Chemistry, Kaduna PolytechnicChemistry Department, Ahmadu Bello UniversityChemistry Department, Ahmadu Bello UniversityAbstract Backgrond In silico studies are essential techniques in the modern medicinal chemistry. QSAR modeling and molecular docking are important techniques in both drug discovery and development and have been successfully deployed in the field of medicinal chemistry for the discovery, design, and development of many drug candidates. These techniques were used in this work to come up with a model that relate 2,5-disubstituted furans with their antiplasmodium activities for the development of more active antimalarial drugs. Results Predictive and robust QSAR model was generated using Genetic Function Algorithm. The model was statistically validated to have internal and external squared correlation coefficient, R 2 of 0.982 and 0.735 respectively; predictive squared correlation coefficient, R 2 pred of 0.599; adjusted squared correlation coefficient, R adj of 0.974; and leave-one-out cross-validation coefficient, Q 2 cv of 0.966. It was found out that the antiplasmodium activities of 2,5-disubstituted furans relied on the parameters: GATS5c, minsCl RDF130m, RDF75p, and RDF115s descriptors. All the descriptors except minsCl influenced the antiplasmodium activities of the compounds negatively. That is, their increase decreases the activities of the furans and vice versa. The docking study revealed that most of the furans bind more tightly to Plasmodium falciparum lactate dehydrogenase (pfLDH) than chloroquine, but the enzyme may not be their major target. Conclusion Insight into the relationship between 2,5-disubstituted furans and their antiplasmodium activities has been revealed from the results of this work. Therefore, this could serve as a model for designing novel 2,5-disubstituted furans as potential antimalarial drugs with better activities.http://link.springer.com/article/10.1186/s42269-020-00333-9AntimalariaQSARMolecular dockingPlasmodium falciparum lactate dehydrogenaseFuransIn silico studies |
| spellingShingle | Aliyu Wappah Mahmud Gideon Adamu Shallangwa Adamu Uzairu In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates Bulletin of the National Research Centre Antimalaria QSAR Molecular docking Plasmodium falciparum lactate dehydrogenase Furans In silico studies |
| title | In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates |
| title_full | In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates |
| title_fullStr | In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates |
| title_full_unstemmed | In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates |
| title_short | In silico studies of 2,5-disubstituted furans as active antimalarial drug candidates |
| title_sort | in silico studies of 2 5 disubstituted furans as active antimalarial drug candidates |
| topic | Antimalaria QSAR Molecular docking Plasmodium falciparum lactate dehydrogenase Furans In silico studies |
| url | http://link.springer.com/article/10.1186/s42269-020-00333-9 |
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