| Texto completo | |
| Autor(es): |
Grigolo, Thiago A.
[1]
;
Braga, Carolyne B.
[1]
;
Ornelas, Catia
[1]
;
Russowsky, Dennis
[2]
;
Ferreira-Silva, Guilherme A.
[3]
;
Ionta, Marisa
[3]
;
Pilli, Ronaldo A.
[1]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, UNICAMP, BR-13083970 Campinas, SP - Brazil
[2] Univ Fed Rio Grande do Sul, Inst Chem, BR-91501970 Porto Alegre, RS - Brazil
[3] Univ Fed Alfenas, Inst Biomed Sci, UNIFAL MG, BR-37130001 Alfenas, MG - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOORGANIC CHEMISTRY; v. 116, NOV 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
A library of nine hybrids of 4-hydroxygoniothalamin (2), 4-hydroxypiplartine (4), monastrol (5) and oxomonastrol (6) was prepared via a modular synthetic route with a diester or a 1,2,3-triazole as linkers. The compounds were assayed against a panel of human cancer cell lines, including MCF-7 (breast adenocarcinoma), HeLa (cervical adenocarcinoma), Caco-2 (colorectal adenocarcinoma) and PC3 (prostate adenocarcinoma), as well as against normal breast (MCF10A) and prostate (PNT2) cells. In general, hybrids with an ester linker containing 4-hydroxypiplartine (4) were more potent than the corresponding hybrids with 4-hydroxygoniothalamin (2). On the other hand, compounds presenting the 1,2,3-triazole linker displayed enhanced cytotoxicity and selectivity when compared to their corresponding hybrids with the diester linker. The 4-hydroxypiplartinebased hybrids 12 and 22 displayed high cytotoxicity (IC50 values below 10 mu M) against all cancer cells studied, especially in MCF-7 cells with IC50 values of 1.7 +/- 0.1 and 1.6 +/- 0.9 mu M, respectively. Furthermore, the 4hydroxygoniothalamin-monastrol hybrid (compound 21) and the 4-hydroxypiplartine-oxo-monastrol hybrid (compound 25), both bearing a 1,2,3-triazole linker, displayed high selectivity and potency towards breast cancer cell line (MCF-7 vs. MCF10 cells, selectivity index = 15.8 and 7.1, respectively), while the 4-hydroxypiplartine -4-hydroxymethylgoniothalamin hybrid with a diester linker (compound 33) showed high selectivity towards melanoma cancer cells (selectivity index = 9.6). Antiproliferative and pro-apoptotic potential of compounds 12 and 22 against MCF-7 cancer cells were further investigated. Cell cycle studies revealed increased G2/ M population in MCF-7 cultures as well as reduced G0/G1 population compared to the control groups indicating cell cycle arrest in G2/M phase. In addition, the frequency of positive cells for annexin V was higher in treated samples suggesting that compounds 12 and 22 induce apoptosis in estrogen-positive MCF-7 cells. (AU) | |
| Processo FAPESP: | 17/06146-8 - Desenvolvimento de nanocarregadores baseados em dendrímeros e nanopartículas poliméricas para a vetorização seletiva da goniotalamina, piplartina e monastrol |
| Beneficiário: | Carolyne Brustolin Braga |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 18/02093-0 - Desenvolvimento de novos nanomateriais para aplicações em nanomedicina |
| Beneficiário: | Cátia Cristina Capêlo Ornelas Megiatto |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas |
| Beneficiário: | Licio Augusto Velloso |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 19/13104-5 - Planejamento e síntese de inibidores baseado em alvo biológico: o caso das quinases negligenciadas |
| Beneficiário: | Ronaldo Aloise Pilli |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |