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Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage
Falcipain-2 (FP2) is a papain family cysteine protease and a key member of the hemoglobin degradation pathway, a process that is required at erythrocytic stages of Plasmodium falciparum to obtain amino acids. In this study, we report a set of 10 quinoline-triazole-based compounds (T1–T10) which exhi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076119/ https://www.ncbi.nlm.nih.gov/pubmed/35540629 http://dx.doi.org/10.1039/c9ra06571g |
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author | Singh, Anju Kalamuddin, Md Mohmmed, Asif Malhotra, Pawan Hoda, Nasimul |
author_facet | Singh, Anju Kalamuddin, Md Mohmmed, Asif Malhotra, Pawan Hoda, Nasimul |
author_sort | Singh, Anju |
collection | PubMed |
description | Falcipain-2 (FP2) is a papain family cysteine protease and a key member of the hemoglobin degradation pathway, a process that is required at erythrocytic stages of Plasmodium falciparum to obtain amino acids. In this study, we report a set of 10 quinoline-triazole-based compounds (T1–T10) which exhibit a good binding affinity for FP2, inhibit its catalytic activity at micromolar concentrations and thereby arrest the parasite growth. Compounds T4 and T7 inhibited FP2 with IC(50) values of 16.16 μM and 25.64 μM respectively. Both the compounds T4 and T7 arrested the development of P. falciparum at the trophozoite stage with an EC(50) value 21.89 μM and 49.88 μM. These compounds also showed morphological and food-vacuole abnormalities like E-64, a known inhibitor of FP2. Our results thus identify the quinoline-triazole-based compounds as a probable starting point for the design of FP2 inhibitors and they should be further investigated as potential antimalarial agents. |
format | Online Article Text |
id | pubmed-9076119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90761192022-05-09 Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage Singh, Anju Kalamuddin, Md Mohmmed, Asif Malhotra, Pawan Hoda, Nasimul RSC Adv Chemistry Falcipain-2 (FP2) is a papain family cysteine protease and a key member of the hemoglobin degradation pathway, a process that is required at erythrocytic stages of Plasmodium falciparum to obtain amino acids. In this study, we report a set of 10 quinoline-triazole-based compounds (T1–T10) which exhibit a good binding affinity for FP2, inhibit its catalytic activity at micromolar concentrations and thereby arrest the parasite growth. Compounds T4 and T7 inhibited FP2 with IC(50) values of 16.16 μM and 25.64 μM respectively. Both the compounds T4 and T7 arrested the development of P. falciparum at the trophozoite stage with an EC(50) value 21.89 μM and 49.88 μM. These compounds also showed morphological and food-vacuole abnormalities like E-64, a known inhibitor of FP2. Our results thus identify the quinoline-triazole-based compounds as a probable starting point for the design of FP2 inhibitors and they should be further investigated as potential antimalarial agents. The Royal Society of Chemistry 2019-11-29 /pmc/articles/PMC9076119/ /pubmed/35540629 http://dx.doi.org/10.1039/c9ra06571g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Singh, Anju Kalamuddin, Md Mohmmed, Asif Malhotra, Pawan Hoda, Nasimul Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title | Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title_full | Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title_fullStr | Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title_full_unstemmed | Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title_short | Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage |
title_sort | quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of plasmodium falciparum at the trophozoite stage |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076119/ https://www.ncbi.nlm.nih.gov/pubmed/35540629 http://dx.doi.org/10.1039/c9ra06571g |
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