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Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents
The challenges concerning the control of malaria remain due to the continuous emergence of drug resistant strains. Over the years, the use, misuse, and abuse of antimalarials have created a conducive environment for the development of resistant Plasmodium falciparum strains. We herein report on the...
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| Language: | English |
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Elsevier
2023
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| _version_ | 1867613139107840000 |
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| access_status_str | Open Access |
| author | Brobbey, A. Addotey, J. N. Danquah, C. A. et al. |
| author_browse | Addotey, J. N. Brobbey, A. Danquah, C. A. et al. |
| author_facet | Brobbey, A. Addotey, J. N. Danquah, C. A. et al. |
| author_sort | Brobbey, A. |
| collection | Thesis |
| description | The challenges concerning the control of malaria remain due to the continuous emergence of drug resistant strains. Over the years, the use, misuse, and abuse of antimalarials have created a conducive environment for the development of resistant Plasmodium falciparum strains. We herein report on the synthesis, characterization and antimalarial activity of a library of seven novel 1,2,3-triazoles as part of the drug discovery campaign against drug-resistant Plasmodium falciparum. The interactions of the triazoles with plasmepsin II, plasmepsin IV, falcipain-2 and the heme detoxifying protein-all key proteins of Plasmodium falciparum degradosequesterome (Dsq) were also investigated by molecular docking. The compounds 3a-d, 4–6 were synthesized by CuAAC click reaction in good to excellent yields of 73–98% and characterized by melting point, UVvisible, infrared and nuclear magnetic resonance (1H and 13C) and MS techniques. Compounds 3a-d displayed high in vitro potency (IC50s: 0.62–22.11 ug/ml) against the chloroquine-resistant Dd2 lab strain of Plasmodium falciparum and low toxicity (SI > 1 except compound 4) to human erythrocytes. Computational studies indicated that the compounds 3a-3d had an absorption of 76–91%, and they were category III acute oral toxins (LD50 from 500 to 5000 mg/kg). The molecular docking study suggests that compounds 3a-d interacted with plasmepsin IV and the heme detoxifying protein with high affinity and a moderate affinity for falcipain-2.
Keywords: Antimalarial; Click reaction; Docking; Plasmodium falciparum; Triazoles |
| id | oai:ir.knust.edu.gh:123456789/14570 |
| institution | KNUST (Ghana) |
| language | English |
| last_indexed | 2026-06-10T12:31:23.640Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana) |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| source_str | KNUSTSpace — Kwame Nkrumah University of Science & Technology (Ghana) |
| spelling | oai:ir.knust.edu.gh:123456789/14570 Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents Brobbey, A. Addotey, J. N. Danquah, C. A. et al. The challenges concerning the control of malaria remain due to the continuous emergence of drug resistant strains. Over the years, the use, misuse, and abuse of antimalarials have created a conducive environment for the development of resistant Plasmodium falciparum strains. We herein report on the synthesis, characterization and antimalarial activity of a library of seven novel 1,2,3-triazoles as part of the drug discovery campaign against drug-resistant Plasmodium falciparum. The interactions of the triazoles with plasmepsin II, plasmepsin IV, falcipain-2 and the heme detoxifying protein-all key proteins of Plasmodium falciparum degradosequesterome (Dsq) were also investigated by molecular docking. The compounds 3a-d, 4–6 were synthesized by CuAAC click reaction in good to excellent yields of 73–98% and characterized by melting point, UVvisible, infrared and nuclear magnetic resonance (1H and 13C) and MS techniques. Compounds 3a-d displayed high in vitro potency (IC50s: 0.62–22.11 ug/ml) against the chloroquine-resistant Dd2 lab strain of Plasmodium falciparum and low toxicity (SI > 1 except compound 4) to human erythrocytes. Computational studies indicated that the compounds 3a-3d had an absorption of 76–91%, and they were category III acute oral toxins (LD50 from 500 to 5000 mg/kg). The molecular docking study suggests that compounds 3a-d interacted with plasmepsin IV and the heme detoxifying protein with high affinity and a moderate affinity for falcipain-2. Keywords: Antimalarial; Click reaction; Docking; Plasmodium falciparum; Triazoles 2023-11-09T16:15:51Z 2023-11-09T16:15:51Z 2021-11 Francis Klenam Kekessie, Cedric Dzidzor Kodjo Amengor, Abena Brobbey, John Nii Addotey, Cynthia Amaning Danquah, Paul Peprah, Benjamin Kingsley Harley, Inemesit Okon Ben, Felix Kwame Zoiku, Lawrence Sheringham Borquaye, Edward Ntim Gasu, Ebenezer Ofori-Attah, Michael Tetteh, Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents, Scientific African, Volume 14, 2021, e00998, ISSN 2468-2276, https://doi.org/10.1016/j.sciaf.2021.e00998 https://ir.knust.edu.gh/handle/123456789/14570 en application/pdf Elsevier |
| spellingShingle | Brobbey, A. Addotey, J. N. Danquah, C. A. et al. Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title | Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title_full | Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title_fullStr | Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title_full_unstemmed | Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title_short | Synthesis, molecular docking studies and ADME prediction of some new triazoles as potential antimalarial agents |
| title_sort | synthesis molecular docking studies and adme prediction of some new triazoles as potential antimalarial agents |
| url | https://ir.knust.edu.gh/handle/123456789/14570 |
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