Blood-stage antimalarial activity, favourable metabolic stability and in vivo toxicity of novel piperazine linked 7-chloroquinoline-triazole conjugates
Copyright © 2023 Elsevier Masson SAS. All rights reserved..
The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:264 |
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| Enthalten in: |
European journal of medicinal chemistry - 264(2024) vom: 15. Jan., Seite 115969 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Uddin, Amad [VerfasserIn] |
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| Links: |
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| Themen: |
1RTM4PAL0V |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 01.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2023.115969 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM365307823 |
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| 245 | 1 | 0 | |a Blood-stage antimalarial activity, favourable metabolic stability and in vivo toxicity of novel piperazine linked 7-chloroquinoline-triazole conjugates |
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| 520 | |a Copyright © 2023 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antimalarials | |
| 650 | 4 | |a Blood-stage | |
| 650 | 4 | |a Falcipain | |
| 650 | 4 | |a Hemozoin inhibition | |
| 650 | 4 | |a In vivo | |
| 650 | 4 | |a Metabolic stability | |
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| 650 | 7 | |a Piperazine |2 NLM | |
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| 700 | 1 | |a Gupta, Sonal |e verfasserin |4 aut | |
| 700 | 1 | |a Shoaib, Rumaisha |e verfasserin |4 aut | |
| 700 | 1 | |a Aneja, Babita |e verfasserin |4 aut | |
| 700 | 1 | |a Irfan, Iram |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Kanika |e verfasserin |4 aut | |
| 700 | 1 | |a Rawat, Neha |e verfasserin |4 aut | |
| 700 | 1 | |a Combrinck, Jill |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Bhumika |e verfasserin |4 aut | |
| 700 | 1 | |a Aleem, Mohd |e verfasserin |4 aut | |
| 700 | 1 | |a Hasan, Phool |e verfasserin |4 aut | |
| 700 | 1 | |a Joshi, Mukesh C |e verfasserin |4 aut | |
| 700 | 1 | |a Chhonker, Yashpal S |e verfasserin |4 aut | |
| 700 | 1 | |a Zahid, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Hussain, Afzal |e verfasserin |4 aut | |
| 700 | 1 | |a Pandey, Kailash |e verfasserin |4 aut | |
| 700 | 1 | |a Alajmi, Mohamed F |e verfasserin |4 aut | |
| 700 | 1 | |a Murry, Daryl J |e verfasserin |4 aut | |
| 700 | 1 | |a Egan, Timothy J |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Shailja |e verfasserin |4 aut | |
| 700 | 1 | |a Abid, Mohammad |e verfasserin |4 aut | |
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