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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/24/5941 |
| Summary: | 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. |
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| ISSN: | 1420-3049 |