<em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development
The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial ac...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/8/1197 |
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| author | Benedito M. dos Santos Daniel T. G. Gonzaga Fernando C. da Silva Vitor F. Ferreira Celia R. S. Garcia |
| author_facet | Benedito M. dos Santos Daniel T. G. Gonzaga Fernando C. da Silva Vitor F. Ferreira Celia R. S. Garcia |
| author_sort | Benedito M. dos Santos |
| collection | DOAJ |
| description | The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite <i>Plasmodium falciparum</i> in a culture of fifty-four triazole compounds derived from 1<i>H</i>-and 2<i>H</i>-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC<sub>50</sub> values ranging from 2.80 µM (<b>9</b>) to 29.27 µM (<b>21</b>). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for <i>P. falciparum</i> G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC<sub>50</sub> values for the knockout strain. The cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (<b>9</b>, <b>13</b>, <b>19</b>, <b>22</b>, <b>24</b>, <b>29</b>), showed no toxicity at the tested concentrations. |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T17:16:28Z |
| publishDate | 2020-08-01 |
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| series | Biomolecules |
| spelling | doaj.art-a21cbc37fc824d03a15daf2b79ff2c1d2023-11-20T10:29:15ZengMDPI AGBiomolecules2218-273X2020-08-01108119710.3390/biom10081197<em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite DevelopmentBenedito M. dos Santos0Daniel T. G. Gonzaga1Fernando C. da Silva2Vitor F. Ferreira3Celia R. S. Garcia4Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo-SP 05508-000, BrazilFundação Centro Universitário Estadual da Zona Oeste, Unidade de Farmácia, Rio de Janeiro-RJ 23070-200, BrazilDepartment of Organic Chemistry, Institute of Chemistry, Universidade Federal Fluminense, Niterói-RJ 24220-900, BrazilDepartment of Pharmaceutical Technology, Pharmacy School, Universidade Federal Fluminense, Niterói-RJ 24220-900, BrazilDepartment of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo-SP 05508-000, BrazilThe search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite <i>Plasmodium falciparum</i> in a culture of fifty-four triazole compounds derived from 1<i>H</i>-and 2<i>H</i>-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC<sub>50</sub> values ranging from 2.80 µM (<b>9</b>) to 29.27 µM (<b>21</b>). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for <i>P. falciparum</i> G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC<sub>50</sub> values for the knockout strain. The cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (<b>9</b>, <b>13</b>, <b>19</b>, <b>22</b>, <b>24</b>, <b>29</b>), showed no toxicity at the tested concentrations.https://www.mdpi.com/2218-273X/10/8/1197antimalarialG-protein coupled receptorheterocyclesPfSR25<i>Plasmodium falciparum</i>screening |
| spellingShingle | Benedito M. dos Santos Daniel T. G. Gonzaga Fernando C. da Silva Vitor F. Ferreira Celia R. S. Garcia <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development Biomolecules antimalarial G-protein coupled receptor heterocycles PfSR25 <i>Plasmodium falciparum</i> screening |
| title | <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development |
| title_full | <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development |
| title_fullStr | <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development |
| title_full_unstemmed | <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development |
| title_short | <em>Plasmodium falciparum</em> Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development |
| title_sort | em plasmodium falciparum em knockout for the gpcr like pfsr25 receptor displays greater susceptibility to 1 2 3 triazole compounds that block malaria parasite development |
| topic | antimalarial G-protein coupled receptor heterocycles PfSR25 <i>Plasmodium falciparum</i> screening |
| url | https://www.mdpi.com/2218-273X/10/8/1197 |
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