Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies
The potency of 1,3,5-trisubstituted pyrazoline as an antimalarial agent has been studied through quantitative structure-activity relationship, molecular docking, and molecular dynamics simulation as a combination of in silico studies. The study commenced by applying quantitative structure-activity r...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Penerbit Universiti Kebangsaan Malaysia
2023
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| Online Access: | http://journalarticle.ukm.my/23331/ http://journalarticle.ukm.my/23331/1/SS%2010.pdf |
| _version_ | 1848815818042769408 |
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| author | Rasyid, Herlina Soekamto, Nunuk Hariani Firdausiah, Syadza Mardiyanti, Riska Bahrun, Siswanto, Aswad, Muhammad Saputri, Wahyu Dita Suma, Artania A. T. Nur Hilal Syahrir, Listyarini, Risnita Vicky |
| author_facet | Rasyid, Herlina Soekamto, Nunuk Hariani Firdausiah, Syadza Mardiyanti, Riska Bahrun, Siswanto, Aswad, Muhammad Saputri, Wahyu Dita Suma, Artania A. T. Nur Hilal Syahrir, Listyarini, Risnita Vicky |
| author_sort | Rasyid, Herlina |
| building | UKM Institutional Repository |
| collection | Online Access |
| description | The potency of 1,3,5-trisubstituted pyrazoline as an antimalarial agent has been studied through quantitative structure-activity relationship, molecular docking, and molecular dynamics simulation as a combination of in silico studies. The study commenced by applying quantitative structure-activity relationship (QSAR) to 25 derivative compounds using 3D-descriptor. The genetic algorithm and multiple linear regression analysis were used to construct the QSAR model, which resulting an equation that has Rtraining as 0.8100 and Rtest set as 0.9222. Descriptors involved in the QSAR equation are TDB4 m, TDB8s, RDF30e, and RDF552, all of which belong to the group of 3D autocorrelation and RDF. This result is in line with the principal component analysis, which shows that both group descriptors represent whole 3D descriptors. Molecular docking analysis is conducted to study the interaction between pyrazoline derivatives and the falcipain-2 enzyme. Interactions between compound 14 and falcipain-2 is describing by hydrogen bond against Glu14 amino acid residue, more pi-stacking interaction, and van der Waals. Chloroquine as a positive control also presented one hydrogen bond with Gly83, pi-sulfur against Cys42, and van der Waals. The stability of the ligand– enzyme interaction is evaluated by molecular dynamics simulation, and after 100 ns simulations, the root mean square deviation results show that compound 14 and chloroquine have a stable interaction with the falcipain-2 enzyme. Overall, this research provides the insight of 1,3,5-trisubstitued pyrazoline compounds as antimalaria by giving a QSAR equation and used to design a better falcipain-2 inhibitors. |
| first_indexed | 2025-11-15T00:56:01Z |
| format | Article |
| id | oai:generic.eprints.org:23331 |
| institution | Universiti Kebangasaan Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T00:56:01Z |
| publishDate | 2023 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | oai:generic.eprints.org:233312024-04-03T01:16:39Z http://journalarticle.ukm.my/23331/ Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies Rasyid, Herlina Soekamto, Nunuk Hariani Firdausiah, Syadza Mardiyanti, Riska Bahrun, Siswanto, Aswad, Muhammad Saputri, Wahyu Dita Suma, Artania A. T. Nur Hilal Syahrir, Listyarini, Risnita Vicky The potency of 1,3,5-trisubstituted pyrazoline as an antimalarial agent has been studied through quantitative structure-activity relationship, molecular docking, and molecular dynamics simulation as a combination of in silico studies. The study commenced by applying quantitative structure-activity relationship (QSAR) to 25 derivative compounds using 3D-descriptor. The genetic algorithm and multiple linear regression analysis were used to construct the QSAR model, which resulting an equation that has Rtraining as 0.8100 and Rtest set as 0.9222. Descriptors involved in the QSAR equation are TDB4 m, TDB8s, RDF30e, and RDF552, all of which belong to the group of 3D autocorrelation and RDF. This result is in line with the principal component analysis, which shows that both group descriptors represent whole 3D descriptors. Molecular docking analysis is conducted to study the interaction between pyrazoline derivatives and the falcipain-2 enzyme. Interactions between compound 14 and falcipain-2 is describing by hydrogen bond against Glu14 amino acid residue, more pi-stacking interaction, and van der Waals. Chloroquine as a positive control also presented one hydrogen bond with Gly83, pi-sulfur against Cys42, and van der Waals. The stability of the ligand– enzyme interaction is evaluated by molecular dynamics simulation, and after 100 ns simulations, the root mean square deviation results show that compound 14 and chloroquine have a stable interaction with the falcipain-2 enzyme. Overall, this research provides the insight of 1,3,5-trisubstitued pyrazoline compounds as antimalaria by giving a QSAR equation and used to design a better falcipain-2 inhibitors. Penerbit Universiti Kebangsaan Malaysia 2023 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/23331/1/SS%2010.pdf Rasyid, Herlina and Soekamto, Nunuk Hariani and Firdausiah, Syadza and Mardiyanti, Riska and Bahrun, and Siswanto, and Aswad, Muhammad and Saputri, Wahyu Dita and Suma, Artania A. T. and Nur Hilal Syahrir, and Listyarini, Risnita Vicky (2023) Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies. Sains Malaysiana, 52 (10). pp. 2855-2867. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol52num10_2023/contentsVol52num10_2023.html |
| spellingShingle | Rasyid, Herlina Soekamto, Nunuk Hariani Firdausiah, Syadza Mardiyanti, Riska Bahrun, Siswanto, Aswad, Muhammad Saputri, Wahyu Dita Suma, Artania A. T. Nur Hilal Syahrir, Listyarini, Risnita Vicky Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title | Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title_full | Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title_fullStr | Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title_full_unstemmed | Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title_short | Revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| title_sort | revealing the potency of 1,3,5-trisubstituted pyrazoline as antimalaria through combination of in silico studies |
| url | http://journalarticle.ukm.my/23331/ http://journalarticle.ukm.my/23331/ http://journalarticle.ukm.my/23331/1/SS%2010.pdf |