Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles
A second generation of 4-aminoquinoline- and 8-aminoquinoline-based tetrazoles and lactams were synthesized via the Staudinger and Ugi multicomponent reactions. These compounds were subsequently evaluated in vitro for their potential antiplasmodium activity against a multidrug-resistant K1 strain an...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/24/5941 |
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| author | Matshawandile Tukulula Stefan Louw Mathew Njoroge Kelly Chibale |
| author_facet | Matshawandile Tukulula Stefan Louw Mathew Njoroge Kelly Chibale |
| author_sort | Matshawandile Tukulula |
| collection | DOAJ |
| description | A second generation of 4-aminoquinoline- and 8-aminoquinoline-based tetrazoles and lactams were synthesized via the Staudinger and Ugi multicomponent reactions. These compounds were subsequently evaluated in vitro for their potential antiplasmodium activity against a multidrug-resistant K1 strain and for their antitrypanosomal activity against a cultured <i>T. b. rhodesiense</i> STIB900 strain. Several of these compounds (<b>4a</b>–<b>g</b>) displayed good antiplasmodium activities (IC<sub>50</sub> = 0.20–0.62 µM) that were comparable to the reference drugs, while their antitrypanosomal activity was moderate (<20 µM). Compound <b>4e</b> was 2-fold more active than primaquine and was also the most active (IC<sub>50</sub> = 7.01 µM) against <i>T. b. rhodesiense</i> and also exhibited excellent aqueous solubility (>200 µM) at pH 7. |
| first_indexed | 2024-03-10T14:02:57Z |
| format | Article |
| id | doaj.art-708eb0e6c9824722ae7a482678023640 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:02:57Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-708eb0e6c9824722ae7a4826780236402023-11-21T00:54:19ZengMDPI AGMolecules1420-30492020-12-012524594110.3390/molecules25245941Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and TetrazolesMatshawandile Tukulula0Stefan Louw1Mathew Njoroge2Kelly Chibale3School of Chemistry and Physics, University of KwaZulu Natal, Durban 4000, South AfricaDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South AfricaDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South AfricaDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South AfricaA second generation of 4-aminoquinoline- and 8-aminoquinoline-based tetrazoles and lactams were synthesized via the Staudinger and Ugi multicomponent reactions. These compounds were subsequently evaluated in vitro for their potential antiplasmodium activity against a multidrug-resistant K1 strain and for their antitrypanosomal activity against a cultured <i>T. b. rhodesiense</i> STIB900 strain. Several of these compounds (<b>4a</b>–<b>g</b>) displayed good antiplasmodium activities (IC<sub>50</sub> = 0.20–0.62 µM) that were comparable to the reference drugs, while their antitrypanosomal activity was moderate (<20 µM). Compound <b>4e</b> was 2-fold more active than primaquine and was also the most active (IC<sub>50</sub> = 7.01 µM) against <i>T. b. rhodesiense</i> and also exhibited excellent aqueous solubility (>200 µM) at pH 7.https://www.mdpi.com/1420-3049/25/24/5941human African trypanosomiasis (HAT)<i>Plasmodium falciparum</i> chloroquine multidrug-resistant (K1) strain4-aminoquinoline β-lactams8-aminoquinoline tetrazolesaqueous kinetic solubility |
| spellingShingle | Matshawandile Tukulula Stefan Louw Mathew Njoroge Kelly Chibale Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles Molecules human African trypanosomiasis (HAT) <i>Plasmodium falciparum</i> chloroquine multidrug-resistant (K1) strain 4-aminoquinoline β-lactams 8-aminoquinoline tetrazoles aqueous kinetic solubility |
| title | Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles |
| title_full | Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles |
| title_fullStr | Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles |
| title_full_unstemmed | Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles |
| title_short | Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles |
| title_sort | synthesis and in vitro antiprotozoan evaluation of 4 8 aminoquinoline based lactams and tetrazoles |
| topic | human African trypanosomiasis (HAT) <i>Plasmodium falciparum</i> chloroquine multidrug-resistant (K1) strain 4-aminoquinoline β-lactams 8-aminoquinoline tetrazoles aqueous kinetic solubility |
| url | https://www.mdpi.com/1420-3049/25/24/5941 |
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