Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds
A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c–3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P...
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| Format: | Article |
| Language: | English |
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American Chemical Society
2022
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| Online Access: | https://doi.org/10.1021/ml400311r http://hdl.handle.net/11408/4922 |
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| author | Tukulula, Matshawandile Njoroge, Mathew Abay, Efrem T. Mugumbate, Grace C. Wiesner, Lubbe Taylor, Dale Gibhard, Liezl Norman, Jennifer Swart, Kenneth J. Gut, Jiri Rosenthal, Philip J. Barteau, Samuel Streckfuss, Judith Kameni-Tcheudji, Jacques Chibale, Kelly |
| author_facet | Tukulula, Matshawandile Njoroge, Mathew Abay, Efrem T. Mugumbate, Grace C. Wiesner, Lubbe Taylor, Dale Gibhard, Liezl Norman, Jennifer Swart, Kenneth J. Gut, Jiri Rosenthal, Philip J. Barteau, Samuel Streckfuss, Judith Kameni-Tcheudji, Jacques Chibale, Kelly |
| author_sort | Tukulula, Matshawandile |
| collection | DSpace |
| description | A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c–3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4–6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7. |
| format | Article |
| id | ir-11408-4922 |
| institution | My University |
| language | English |
| publishDate | 2022 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | ir-11408-49222022-06-28T12:30:04Z Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds Tukulula, Matshawandile Njoroge, Mathew Abay, Efrem T. Mugumbate, Grace C. Wiesner, Lubbe Taylor, Dale Gibhard, Liezl Norman, Jennifer Swart, Kenneth J. Gut, Jiri Rosenthal, Philip J. Barteau, Samuel Streckfuss, Judith Kameni-Tcheudji, Jacques Chibale, Kelly Aminoquinolines antiplasmodial activity pharmacokinetics Plasma protein binding A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c–3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4–6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7. 2022-06-28T12:30:04Z 2022-06-28T12:30:04Z 2013 Article 1948-5875 https://doi.org/10.1021/ml400311r http://hdl.handle.net/11408/4922 en ACS Medicinal Chemistry Letters;Volume 4, No. 12; pages 1198-1202 open American Chemical Society |
| spellingShingle | Aminoquinolines antiplasmodial activity pharmacokinetics Plasma protein binding Tukulula, Matshawandile Njoroge, Mathew Abay, Efrem T. Mugumbate, Grace C. Wiesner, Lubbe Taylor, Dale Gibhard, Liezl Norman, Jennifer Swart, Kenneth J. Gut, Jiri Rosenthal, Philip J. Barteau, Samuel Streckfuss, Judith Kameni-Tcheudji, Jacques Chibale, Kelly Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title | Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title_full | Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title_fullStr | Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title_full_unstemmed | Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title_short | Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds |
| title_sort | synthesis and in vitro and in vivo pharmacological evaluation of new 4-aminoquinoline-based compounds |
| topic | Aminoquinolines antiplasmodial activity pharmacokinetics Plasma protein binding |
| url | https://doi.org/10.1021/ml400311r http://hdl.handle.net/11408/4922 |
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