A primaquine–chloroquine hybrid with dual activity against Plasmodium liver and blood stages

Lödige, Melanie; Lewis, Matthew D.; Paulsen, Eleonora S.; Esch, Harald L.; Pradel, Gabriele; Lehmann, Leane; Brun, Reto; Bringmann, Gerhard; Mueller, Ann‐Kristin

doi:10.1016/j.ijmm.2013.07.005

Cited by 33 publications

(22 citation statements)

References 49 publications

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“…they would show their activity in blood as well as liver stage [88,89]. In this direction, Lödige [90] Figure 25). According to the invention, patient suffering from relapse malaria can be successfully treated with this combination within six days.…”

Section: Q-l-gmentioning

confidence: 87%

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Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Mushtaque¹,

Shahjahan²

2015

European Journal of Medicinal Chemistry

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Section: Q-l-gmentioning

confidence: 87%

“…This aim was achieved by N-cinnamoylation of CQ [88] and conjugation of CQ with PQ [90]. Moreover, some reported molecules (Schiff's bases of CQ) were even suggested as the drugs for 21 st century [69].…”

Section: Future Perspectivesmentioning

confidence: 99%

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Mushtaque¹,

Shahjahan²

2015

European Journal of Medicinal Chemistry

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“…Therefore, hybrid structures of primaquine ( 1 ) and a chloroquine moiety ( 3 ) were synthesized with a linker using original side chain of primaquine, with a pharmacophore ratio of 1 : 1 and 1 : 2 of primaquine ( 1 ) to chloroquine ( 2 ). Since a Buchwald-Hartwig amination protocol leads merely to low yields (a decomposition of the palladium catalyst was observed), a nucleophilic substitution reaction of primaquine ( 1 ) and 4,7-dichloroquinoline was performed at 120°C under neat conditions to obtain the hybrid molecules ( rac )- 5 (82% yield) and ( rac )- 6 (77%, Scheme 1 ) [ 57 ].…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Novel Hybrid Molecules against Malaria

Lödige

Hiersch

2015

International Journal of Medicinal Chemistry

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The effective treatment of malaria can be very complex: Plasmodium parasites develop in multiple stages within a complex life cycle between mosquitoes as vectors and vertebrates as hosts. For the full and effective elimination of parasites, an effective drug should be active against the earliest stages of the Plasmodium infection: liver stages (reduce the progress of the infection), blood stages (cure the clinical symptoms), and gametocytes (inhibit the transmission cycle). Towards this goal, here we report the design, the synthetic methodology, and the characterization of novel hybrid agents with combined activity against Plasmodium liver stages and blood stages and gametocytes. The divergent synthetic approach allows the access to differently linked primaquine-chloroquine hybrid templates in up to eight steps.

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“…Primaquine-chloroquine conjugate 169 was obtained by heating of primaquine with 4,7-dichloroquinoline (Scheme 11) [127].…”

Section: Primaquine-chloroquine Conjugatementioning

confidence: 99%

Primaquine derivatives: Modifications of the terminal amino group

Zorc

Perković

Rajić

et al. 2019

European Journal of Medicinal Chemistry

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a b s t r a c tNumerous modifications of the well-known antimalarial drug primaquine, both at the quinoline ring and at the primary amino group, have been reported, mostly to obtain antimalarial agents with improved bioavailability, reduced toxicity and/or prolonged activity. Modifications of the terminal amino group were made with the main idea to prevent the metabolic pathway leading to inactive and toxic carboxyprimaquine (follow-on strategy), but also to get compounds with different activity (repurposing strategy). The modifications undertaken until 2009 were included in a review published in the same year. The present review covers various classes of primaquine N-derivatives with diverse biological profiles, prepared in the last decade by our research group as well as the others. We have summarized the synthetic procedures applied for their preparation and discussed the main biological results. Several hits for the development of novel antiplasmodial, anticancer, antimycobacterial and antibiofilm agents were identified.

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A primaquine–chloroquine hybrid with dual activity against Plasmodium liver and blood stages

Cited by 33 publications

References 49 publications

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Design and Synthesis of Novel Hybrid Molecules against Malaria

Primaquine derivatives: Modifications of the terminal amino group

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