In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum
Abstract Background Despite advances in malaria chemotherapy, the disease continues to claim thousands of lives annually. Addressing this issue requires the discovery of new compounds to counteract resistance threatening the current therapeutic arsenal. In this context, bi-triazoles are substances w...
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2025-03-01
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| Online Access: | https://doi.org/10.1186/s12936-025-05297-7 |
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| author | Leandro do Nascimento Martinez Minelly Azevedo da Silva Saara Neri Fialho Marcinete Latorre Almeida Amália dos Santos Ferreira Aurileya de Jesus Gouveia Welington da Silva Paula do Nascimento Ana Paula de Azevedo dos Santos Norton Rubens Diunior Lucas Pejara Rossi Jansen Fernandes de Medeiros Natalie Ferreira Araújo Quelli Larissa Oliveira de Santana Carlos Roland Kaiser Sabrina Baptista Ferreira Maisa da Silva Araujo Carolina Bioni Garcia Teles |
| author_facet | Leandro do Nascimento Martinez Minelly Azevedo da Silva Saara Neri Fialho Marcinete Latorre Almeida Amália dos Santos Ferreira Aurileya de Jesus Gouveia Welington da Silva Paula do Nascimento Ana Paula de Azevedo dos Santos Norton Rubens Diunior Lucas Pejara Rossi Jansen Fernandes de Medeiros Natalie Ferreira Araújo Quelli Larissa Oliveira de Santana Carlos Roland Kaiser Sabrina Baptista Ferreira Maisa da Silva Araujo Carolina Bioni Garcia Teles |
| author_sort | Leandro do Nascimento Martinez |
| collection | DOAJ |
| description | Abstract Background Despite advances in malaria chemotherapy, the disease continues to claim thousands of lives annually. Addressing this issue requires the discovery of new compounds to counteract resistance threatening the current therapeutic arsenal. In this context, bi-triazoles are substances with diverse biological activities, showing promise as lead compound to fight malaria. Triazoles are heterocyclic structures composed of five members, including three nitrogen atoms and two double bonds. Bi-triazoles, the focus of this study, are derivatives of triazoles consisting of two triazole rings (nitrogen heterocyclic) with isolated nuclei lacking a spacer and two substituents at each end. The goal of the present study was to assess the in vitro and in silico, antimalarial activity of bi-triazole compounds 14c, 14d, 13c, and 13d against asexual and sexual forms of Plasmodium falciparum. Methods For in silico predictions, the software OSIRIS, Molinspiration, and ADMETlab were employed. To determine the 50% inhibitory concentration (IC50) on the asexual forms, the W2 clone was used, while the strain NF54 was used to assess inhibition of sexual forms. Cytotoxicity was evaluated using the HepG2 cell line, and haemolysis tests were conducted. Additionally, the selectivity index (SI) of each compound was calculated. Results In silico analyses of physicochemical properties revealed that all compounds have favorable potential for drug development. Pharmacokinetics predictions also provided important, novel insights into this chemical class. Antimalarial activity tests showed that compounds 14d and 13d exhibited promising activity, with IC50 values of 3.1 and 4.4 µM, respectively. Antimalarial activity of compounds 14d and 13d may be related to the presence of methyl acetate in substituent R2 conjugated to the bi-triazole. None of the compounds demonstrated cytotoxic or haemolytic activity, with SI values above 51 for the three most active compounds, highlighting their selectivity. For the sexual forms, compounds 14c and 14d were classified as having a high potential to block malaria transmission. Conclusion Overall, the in vitro and in silico results showed that bi-triazole compounds may guide new biological investigation for malaria, enabling the identification and development of more active and selective antimalarial agents. |
| format | Article |
| id | doaj-art-953ce8d9fe974423ac077e19d7930232 |
| institution | DOAJ |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj-art-953ce8d9fe974423ac077e19d79302322025-08-20T03:05:57ZengBMCMalaria Journal1475-28752025-03-0124111410.1186/s12936-025-05297-7In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparumLeandro do Nascimento Martinez0Minelly Azevedo da Silva1Saara Neri Fialho2Marcinete Latorre Almeida3Amália dos Santos Ferreira4Aurileya de Jesus Gouveia5Welington da Silva Paula do Nascimento6Ana Paula de Azevedo dos Santos7Norton Rubens Diunior Lucas Pejara Rossi8Jansen Fernandes de Medeiros9Natalie Ferreira Araújo10Quelli Larissa Oliveira de Santana11Carlos Roland Kaiser12Sabrina Baptista Ferreira13Maisa da Silva Araujo14Carolina Bioni Garcia Teles15Plataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaInstituto Federal de Educação, Ciência e Tecnologia de Rondônia – IFROPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaCentro Universitário São Lucas -PVH/AfyaPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaPrograma de Pós-Graduação Em Biologia Experimental (PGBIOEXP), Fundação Universidade Federal de Rondônia (UNIR)LaSOPB – Laboratório de Síntese Orgânica e Prospecção Biológica, InstitutodeQuímica, Universidade Federal Do Rio de JaneiroLaSOPB – Laboratório de Síntese Orgânica e Prospecção Biológica, InstitutodeQuímica, Universidade Federal Do Rio de JaneiroLaSOPB – Laboratório de Síntese Orgânica e Prospecção Biológica, InstitutodeQuímica, Universidade Federal Do Rio de JaneiroLaSOPB – Laboratório de Síntese Orgânica e Prospecção Biológica, InstitutodeQuímica, Universidade Federal Do Rio de JaneiroPrograma de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal – BIONORTEPlataforma de Bioensaios de Malária E Leishmaniose (PBML), Fundação Oswaldo Cruz, FIOCRUZ, Unidade RondôniaAbstract Background Despite advances in malaria chemotherapy, the disease continues to claim thousands of lives annually. Addressing this issue requires the discovery of new compounds to counteract resistance threatening the current therapeutic arsenal. In this context, bi-triazoles are substances with diverse biological activities, showing promise as lead compound to fight malaria. Triazoles are heterocyclic structures composed of five members, including three nitrogen atoms and two double bonds. Bi-triazoles, the focus of this study, are derivatives of triazoles consisting of two triazole rings (nitrogen heterocyclic) with isolated nuclei lacking a spacer and two substituents at each end. The goal of the present study was to assess the in vitro and in silico, antimalarial activity of bi-triazole compounds 14c, 14d, 13c, and 13d against asexual and sexual forms of Plasmodium falciparum. Methods For in silico predictions, the software OSIRIS, Molinspiration, and ADMETlab were employed. To determine the 50% inhibitory concentration (IC50) on the asexual forms, the W2 clone was used, while the strain NF54 was used to assess inhibition of sexual forms. Cytotoxicity was evaluated using the HepG2 cell line, and haemolysis tests were conducted. Additionally, the selectivity index (SI) of each compound was calculated. Results In silico analyses of physicochemical properties revealed that all compounds have favorable potential for drug development. Pharmacokinetics predictions also provided important, novel insights into this chemical class. Antimalarial activity tests showed that compounds 14d and 13d exhibited promising activity, with IC50 values of 3.1 and 4.4 µM, respectively. Antimalarial activity of compounds 14d and 13d may be related to the presence of methyl acetate in substituent R2 conjugated to the bi-triazole. None of the compounds demonstrated cytotoxic or haemolytic activity, with SI values above 51 for the three most active compounds, highlighting their selectivity. For the sexual forms, compounds 14c and 14d were classified as having a high potential to block malaria transmission. Conclusion Overall, the in vitro and in silico results showed that bi-triazole compounds may guide new biological investigation for malaria, enabling the identification and development of more active and selective antimalarial agents.https://doi.org/10.1186/s12936-025-05297-7Bi-triazolesGametocytesTransmission blockingPlasmodium falciparumIn silico |
| spellingShingle | Leandro do Nascimento Martinez Minelly Azevedo da Silva Saara Neri Fialho Marcinete Latorre Almeida Amália dos Santos Ferreira Aurileya de Jesus Gouveia Welington da Silva Paula do Nascimento Ana Paula de Azevedo dos Santos Norton Rubens Diunior Lucas Pejara Rossi Jansen Fernandes de Medeiros Natalie Ferreira Araújo Quelli Larissa Oliveira de Santana Carlos Roland Kaiser Sabrina Baptista Ferreira Maisa da Silva Araujo Carolina Bioni Garcia Teles In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum Malaria Journal Bi-triazoles Gametocytes Transmission blocking Plasmodium falciparum In silico |
| title | In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum |
| title_full | In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum |
| title_fullStr | In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum |
| title_full_unstemmed | In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum |
| title_short | In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum |
| title_sort | in vitro and in silico evaluation of synthetic compounds derived from bi triazoles against asexual and sexual forms of plasmodium falciparum |
| topic | Bi-triazoles Gametocytes Transmission blocking Plasmodium falciparum In silico |
| url | https://doi.org/10.1186/s12936-025-05297-7 |
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