| Autor: |
Grawe GF; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br., Oliveira KM; Departamento de Química, ICEB, Universidade Federal de Ouro Preto - UFOP, CEP 35400-000, Ouro Preto, MG, Brazil. kmoliveiraq@gmail.com., Leite CM; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br., de Oliveira TD; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br., Honorato J; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br., Ferreira AG; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br., Castellano EE; Instituto de Física de São Carlos, Universidade de São Paulo - USP, CP 369, CEP 13560-970, São Carlos, SP, Brazil., Cominetti MR; Departamento de Gerontologia, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13565-905, São Carlos, SP, Brazil., Correa RS; Departamento de Química, ICEB, Universidade Federal de Ouro Preto - UFOP, CEP 35400-000, Ouro Preto, MG, Brazil. kmoliveiraq@gmail.com., Batista AA; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. daab@ufscar.br.; Instituto de Química, Universidade Federal de Goiás - UFG, CEP 74690-900, Goiânia, GO, Brazil. |
| Abstrakt: |
We have synthesized and characterized three new ruthenium(II) diphosphine complexes containing an acylthiourea ligand, with the general formula [Ru(DPEPhos)(O,S)(bipy)]PF 6 , 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 IC 50 values lie in the micromolar range (0.07-0.70 μM). 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. |
