| Full text | |
| Author(s): |
De Grandis, Rone Aparecido
[1]
;
da Silva dos Santos, Patrick Wellington
[2]
;
de Oliveira, Katia Mara
[3]
;
Tomazela Machado, Ana Rita
[2]
;
Aissa, Alexandre Ferro
[2]
;
Batista, Alzir Azevedo
[3]
;
Greggi Antunes, Lusania Maria
[2]
;
Pavan, Fernando Rogerio
[1]
Total Authors: 8
|
| Affiliation: | [1] Sao Paulo State Univ, Sch Pharmaceut Sci, BR-14800903 Araraquara, SP - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Univ Fed Sao Carlos, Dept Chem, BR-13561901 Sao Carlos, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | BIOORGANIC CHEMISTRY; v. 85, p. 455-468, APR 2019. |
| Web of Science Citations: | 3 |
| Abstract | |
This study describes a series of newly synthesized phosphine/diimine ruthenium complexes containing the lawsone as bioligand with enhanced cytotoxicity against different cancer cells, and apoptosis induction in prostatic cancer cells DU-145. The complexes {[}Ru(law)(N-N)(2)]PF6 where N-N is 2,2'-bipyridine (1) or 1,10-phenanthroline (2) and {[}Ru(law)(dppm)(N-N)]PF6, where dppm means bis(diphenylphosphino)methane, N-N is 2,2'-bipyridine (3) or 1,10-phenanthroline (4), and law is lawsone, were synthesized and fully characterized by elemental analysis, molar conductivity, NMR, UV-vis, IR spectroscopies and cyclic voltammetry. The interaction of the complexes (1-4) with DNA was evaluated by circular dichroism, gel electrophoresis, and fluorescence, and the complexes presented interactions by the minor grooves DNA. The phosphinic series of complexes exhibited a remarkably broad spectrum of anticancer activity with approximately 34-fold higher than cisplatin and 5-fold higher than doxorubicin, inhibiting the growth of 3D tumor spheroids and the ability to retain the colony survival of DU-145 cells. Also, the complex (4) inhibits DU-145 cell adhesion and migration potential indicating antimetastatic properties. The mechanism of its anticancer activity was found to be related to increased reactive oxygen species (ROS) generation, increased the BAX/BCL-2 ratio and subsequent apoptosis induction. Overall, these findings suggested that the complex (4) could be a promising candidate for further evaluation as a chemotherapeutic agent in the prostate cancer treatment. (AU) | |
| FAPESP's process: | 18/00163-0 - Development and search of new antimicrobials against Tuberculosis: from screening to pre-clinical studies in vivo |
| Grantee: | Fernando Rogério Pavan |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/22429-7 - Toxicogenetics evaluation and study of antiproliferative response mechanisms of ruthenium-based metallodrugs containing naphthoquinones ligands in tumor cells growing in conventional and 3D systems |
| Grantee: | Rone Aparecido de Grandis |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 16/16312-0 - CYTOTOXICITY AND MECHANISM OF ACTION OF RUTHENIUM COMPLEXES CONTAINING NATURAL PRODUCTS OR DERIVATIVES |
| Grantee: | Alzir Azevedo Batista |
| Support Opportunities: | Regular Research Grants |