Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives
In this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has a...
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Elsevier
2025-04-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417424001134 |
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| author | Moussa Touré Abdoulaye Gassama Oumar Sambou Christian Cavé Sandrine Cojean |
| author_facet | Moussa Touré Abdoulaye Gassama Oumar Sambou Christian Cavé Sandrine Cojean |
| author_sort | Moussa Touré |
| collection | DOAJ |
| description | In this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfW2) Plasmodium falciparum strains. Compounds 5i and 5c showed promising efficacy against the Pf3D7 strain with IC50 values of 0.25 μM and 0.54 μM, respectively, while compound 5l demonstrated significant activity against the PfW2 strain with an IC50 of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies. |
| format | Article |
| id | doaj-art-c46da4b17bfc4be984d72936ceceaaeb |
| institution | Kabale University |
| issn | 2772-4174 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj-art-c46da4b17bfc4be984d72936ceceaaeb2024-12-06T05:15:10ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742025-04-0113100241Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivativesMoussa Touré0Abdoulaye Gassama1Oumar Sambou2Christian Cavé3Sandrine Cojean4Laboratoire de Chimie et Physique des Matériaux (LCPM), Université Assane Seck de Ziguinchor, BP: 523, Ziguinchor, SenegalLaboratoire de Chimie et Physique des Matériaux (LCPM), Université Assane Seck de Ziguinchor, BP: 523, Ziguinchor, Senegal; Université Paris-Saclay, UMR 8076 CNRS BioCIS, 17 Rue Avenue des Sciences, 91400, Orsay, France; Corresponding author.Laboratoire de Chimie et Physique des Matériaux (LCPM), Université Assane Seck de Ziguinchor, BP: 523, Ziguinchor, SenegalUniversité Paris-Saclay, UMR 8076 CNRS BioCIS, 17 Rue Avenue des Sciences, 91400, Orsay, France; Corresponding author.Université Paris-Saclay, UMR 8076 CNRS BioCIS, 17 Rue Avenue des Sciences, 91400, Orsay, France; Centre National de Référence Du Paludisme, Hôpital Bichat-Claude Bernard, APHP, 75018, Paris, FranceIn this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfW2) Plasmodium falciparum strains. Compounds 5i and 5c showed promising efficacy against the Pf3D7 strain with IC50 values of 0.25 μM and 0.54 μM, respectively, while compound 5l demonstrated significant activity against the PfW2 strain with an IC50 of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.http://www.sciencedirect.com/science/article/pii/S2772417424001134MalariaQuinolineAntimalarialADMEP. falciparumIn silico |
| spellingShingle | Moussa Touré Abdoulaye Gassama Oumar Sambou Christian Cavé Sandrine Cojean Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives European Journal of Medicinal Chemistry Reports Malaria Quinoline Antimalarial ADME P. falciparum In silico |
| title | Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives |
| title_full | Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives |
| title_fullStr | Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives |
| title_full_unstemmed | Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives |
| title_short | Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives |
| title_sort | synthesis and in vitro in silico evaluation of the antimalarial activity of potential amino quinoline derivatives |
| topic | Malaria Quinoline Antimalarial ADME P. falciparum In silico |
| url | http://www.sciencedirect.com/science/article/pii/S2772417424001134 |
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