In vitro and in vivo antitumor activity of a novel carbonyl ruthenium compound, the ct-[RuCl(CO)(dppb)(bipy)]PF-6[dppb=1,4-bis(diphenylphosphine)butane and bipy=2,2'-bipyridine].
This study performed in vitro and in vivo biological assays of the ruthenium (II) compound ct-[RuCl(CO)(dppb)(bipy)]PF6(where, dppb=1,4-bis(diphenylphosphine)butane and bipy=2,2'-bipyridine). The cytotoxic activity of this compound was evaluated against different tumor cell lines (HeLa, human cervical adenocarcinoma; MCF7, human breast adenocarcinoma; MO59J, human glioblastoma; HepG2, hepatocellular carcinoma and B16F10, murine melanoma) and healthy cell line (V79, Chinese hamster lung fibroblasts), by XTT (sodium 2,3'-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-3,4-tetrazolium-bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) method. A syngeneic murine melanoma tumor model (B16F10) was used to evaluate its antitumor activity. Additionally, experiments were performed to assess the interactions with ctDNA (calf thymus DNA) and BSA (bovine serum albumin). The results showed that ct-[RuCl(CO)(dppb)(bipy)]PF6was cytotoxic against all tumor cell lines tested. Furthermore, the compound was more effective against tumor cells compared to the normal cell line, indicating selectivity, especially in B16F10 cells. Significant tumor growth reduction was observed in animals treated with the compound compared to the untreated control. Histopathological analysis of tumor tissue revealed a significant reduction of mitosis in animals treated with the compound compared to the untreated control. In the ctDNA and BSA interaction experiments, the compound in study showed weak interactions with ctDNA and hydrophobic interactions with BSA. The ruthenium compound investigated showed promising results in in vitro and in vivo biological assays.
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil; Laboratório de Mutagênese, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil.
Andréa P
AP
Carnizello
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil.
Marília I F
MI
Barbosa
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil.
Monize
M
Martins
Laboratório de Mutagênese, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil.
Natália H
NH
Ferreira
Laboratório de Mutagênese, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil.
Pollyanna F
PF
Oliveira
Departamento de Medicina Veterinária, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil.
Geórgia M
GM
Magalhães
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil. Electronic address: daab@ufscar.br.
Alzir A
AA
Batista
Laboratório de Mutagênese, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil. Electronic address: denisecrispim2001@yahoo.com.
Denise C
DC
Tavares
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D004247:DNA / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012710:Serum Albumin, Bovine; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA
Antitumor activity; BSA interaction; Carbonyl ruthenium compounds; DNA interaction