Ruthenium(II)/(III) DMSO-Based Complexes of 2-Aminophenyl Benzimidazole with In Vitro and In Vivo Anticancer...

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Cancer Research

Background:

• Ruthenium complexes are explored for anticancer properties.
• Developing novel chemotherapeutics with targeted action and reduced toxicity is crucial.

Purpose of the Study:

• Synthesize and characterize new ruthenium(II/III) complexes.
• Evaluate their anticancer potential and mechanism of action.
• Assess in vitro and in vivo efficacy and toxicity.

Main Methods:

• Synthesis and characterization of ruthenium complexes [RuCl2(DMSO)2(Hapbim)] (1) and [RuCl3(DMSO)(Hapbim)] (2).
• DNA interaction studies using UV-Visible and fluorescence spectroscopy.
• In vitro cytotoxicity assays on MCF7, Caco2, and THLE-2 cell lines.
• In vivo studies using an Ehrlich Ascites Carcinoma (EAC) mouse model.
• Apoptosis and oxidative stress analysis.

Main Results:

• Both complexes demonstrated DNA intercalation.
• Compound (2) exhibited potent in vitro cytotoxicity against cancer cells, with no activity against normal cells.
• In vivo studies showed compound (2) significantly reduced tumor burden with low hepatotoxicity and nephrotoxicity.
• Compound (2) induced apoptosis, cell-cycle arrest at G2/M phase, decreased oxidative stress, and increased antioxidant enzyme levels.

Conclusions:

• Compound (2) is a promising chemotherapeutic candidate with significant anticancer activity and a favorable safety profile.
• The mechanism involves apoptosis induction and modulation of oxidative stress.
• Further investigation into this ruthenium complex for cancer treatment is warranted.