| Texto completo | |
| Autor(es): |
de Paiva, Raphael E. F.
;
Peterson, Erica J.
;
Du, Zhifeng
;
Farrell, Nicholas P.
Número total de Autores: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | DALTON TRANSACTIONS; v. 49, n. 45, p. 10-pg., 2020-12-07. |
| Resumo | |
Gold(i)-phosphine "auranofin-like" compounds have been extensively explored as anticancer agents in the past decade. Although potent cytotoxic agents, the lack of selectivity towards tumorigenic vs. non-tumorigenic cell lines often hinders further application. Here we explore the cytotoxic effects of a series of (R3P)AuL compounds, evaluating both the effect of the basicity and bulkiness of the carrier phosphine (R = Et or Cy), and the leaving group L (Cl(-)vs. dmap). [Au(dmap)(Et3P)](+) had an IC50 of 0.32 mu M against the CEM cell line, with good selectivity in relation to HUVEC. Flow cytometry indicates reduced G1 population and slight accumulation in G2, as opposed to auranofin, which induces a high population of cells with fragmented DNA. Protein expression profile sets [Au(dmap)(Et3P)](+) further apart from auranofin, with proteolytic degradation of caspase-3 and poly(ADP-ribose)-polymerase (PARP), DNA strand-break induced phosphorylation of Chk2 Thr68 and increased p53 ser15 phosphorylation. The cytoxicity and observable biological effects correlate directly with the reactivity trend observed when using the series of gold(i)-phosphine compounds for targeting a model zinc finger, Sp1ZnF3. (AU) | |
| Processo FAPESP: | 18/21537-6 - Aplicações de ligantes imínicos polidentados na modulação da reatividade de íons cobre em doenças relacionadas a inflamação e em reações de acoplamento bio-ortogonais |
| Beneficiário: | Raphael Enoque Ferraz de Paiva |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |