Publicação
Polyaromatic bis(indolyl)methane derivatives with antiprolif-erative and antiparasitic activity
| Resumo: | Bis(indolyl)methanes (BIM) are a class of compounds that has been recognized as an important core in the design of drugs with important pharmacological properties, such as promising anticancer and antiparasitic activity. Here, we explored the biological activity of the BIM core functionalized with different (hetero)aromatic moieties. We synthesized substituted BIM deriva-tives with triphenylamino, N,N-dimethyl-1-naphthylamino and 8-hydroxylquinolyl groups, studied their photophysical properties and evaluated their in vitro antiproliferative and antiparasitic activity. The triphenylamino BIM derivative 2a displayed an IC50 of 3.21, 3.30 and 3.93 μM against Trypanosoma brucei, Leishmania major and HT-29 cancer cell line, respectively. The selectivity index demonstrated that compound 2a was up to 8-fold more active against the parasites and HT-29 than to the heathy cell line MRC-5. Fluorescence microscopy studies with MRC-5 cells and T. brucei parasites incubated with derivative 2a indicates that the compound seems to accumulate in the cell’s mitochondria and in the parasite’s nucleus. In conclusion, the BIM scaffold functional-ized with the triphenylamino moiety proved to be the most promising antiparasitic and anticancer agent of this series. |
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| Autores principais: | Gonçalves, Raquel Costa Raínha |
| Outros Autores: | Peñalver, Pablo; Costa, Susana P. G.; Morales, Juan C.; Raposo, M. Manuela M. |
| Assunto: | African trypanosomiasis Anticancer agent Antiprotozoal agent Bis(indolyl)methane derivatives Leishmaniasis Synthesis Heterocycles Fluorescence microscopy antiproliferative agent Engenharia e Tecnologia::Engenharia Química Saúde de qualidade |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Bis(indolyl)methanes (BIM) are a class of compounds that has been recognized as an important core in the design of drugs with important pharmacological properties, such as promising anticancer and antiparasitic activity. Here, we explored the biological activity of the BIM core functionalized with different (hetero)aromatic moieties. We synthesized substituted BIM deriva-tives with triphenylamino, N,N-dimethyl-1-naphthylamino and 8-hydroxylquinolyl groups, studied their photophysical properties and evaluated their in vitro antiproliferative and antiparasitic activity. The triphenylamino BIM derivative 2a displayed an IC50 of 3.21, 3.30 and 3.93 μM against Trypanosoma brucei, Leishmania major and HT-29 cancer cell line, respectively. The selectivity index demonstrated that compound 2a was up to 8-fold more active against the parasites and HT-29 than to the heathy cell line MRC-5. Fluorescence microscopy studies with MRC-5 cells and T. brucei parasites incubated with derivative 2a indicates that the compound seems to accumulate in the cell’s mitochondria and in the parasite’s nucleus. In conclusion, the BIM scaffold functional-ized with the triphenylamino moiety proved to be the most promising antiparasitic and anticancer agent of this series. |
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