| Full text | |
| Author(s): |
Grawe, Gregory F.
[1]
;
Oliveira, Katia M.
[2]
;
Leite, Celisnolia M.
[1]
;
de Oliveira, Tamires D.
[1]
;
Honorato, Joao
[1]
;
Ferreira, Antonio G.
[1]
;
Castellano, Eduardo E.
[3]
;
Cominetti, Marcia R.
[4]
;
Correa, Rodrigo S.
[2]
;
Batista, Alzir A.
[1, 5]
Total Authors: 10
|
| Affiliation: | [1] Univ Fed Sao Carlos UFSCar, Dept Quim, CP 676, BR-13561901 Sao Carlos, SP - Brazil
[2] Univ Fed Ouro Preto UFOP, ICEB, Dept Quim, BR-35400000 Ouro Preto, MG - Brazil
[3] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil
[4] Univ Fed Sao Carlos UFSCar, Dept Gerontol, CP 676, BR-13565905 Sao Carlos, SP - Brazil
[5] Univ Fed Goias UFG, Inst Quim, BR-74690900 Goiania, Go - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | DALTON TRANSACTIONS; v. 51, n. 4 DEC 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
We have synthesized and characterized three new ruthenium(ii) diphosphine complexes containing an acylthiourea ligand, with the general formula {[}Ru(DPEPhos)(O,S)(bipy)]PF6, where DPEPhos = bis(2-(diphenylphosphino)phenyl)ether, bipy = 2,2'-bipyridine, and O,S = N,N-dimethyl-N'-(benzoyl)thiourea (1), N,N-dimethyl-N'-(furoyl)thiourea (2), and N,N-dimethyl-N'-(thiophenyl)thiourea (3), by several physicochemical techniques. We evaluated the ruthenium complexes for their cytotoxicity against two human cancer cell lines, A549 (lung) and MDA-MB-231 (breast), and two corresponding lines of non-cancer cells, MRC-5 (lung) and MCF-10A (breast). All the complexes are cytotoxic against the cancer cell lines; the IC50 values lie in the micromolar range (0.07-0.70 mu M). Ruthenium complex 1 is more selective (7 times more active) toward lung cancer cells (A549) than toward non-cancer cells (MRC-5) and is 160 times more cytotoxic than cisplatin against A549 cells. Investigations of the mechanism of action of complex 1 in A549 cells demonstrated that it inhibits colony formation and promotes cell cycle arrest in the G1 phase and apoptotic cell death. DNA binding studies revealed that complexes 1-3 interact with the biomolecule via minor grooves. These complexes also interact with human serum albumin (HSA) and have affinity for site I by hydrophobic forces. Therefore, this new class of ruthenium complexes can act as cytotoxic agents, mainly for lung cancer treatment. (AU) | |
| FAPESP's process: | 20/14561-8 - Study in vitro and in vivo of Ru(II) phosphine complexes with anticancer activities |
| Grantee: | Alzir Azevedo Batista |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/15850-0 - X-ray diffraction as a tool in potential drug development |
| Grantee: | Eduardo Ernesto Castellano |
| Support Opportunities: | Research Projects - Thematic Grants |