Interaction of ferrocene appended Ru(II), Rh(III) and Ir(III) dipyrrinato complexes with DNA/protein, molecular docking and antitumor activity

• Published in: European journal of medicinal chemistry 2014-09, Vol.84, p.17-29
• Main Authors: Paitandi, Rajendra Prasad, Gupta, Rakesh Kumar, Singh, Roop Shikha, Sharma, Gunjan, Koch, Biplob, Pandey, Daya Shankar
• Format: Article
• Language: English
• Subjects: Animals; Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cattle; Cell Line, Tumor; Cell Proliferation - drug effects; Crystallography, X-Ray; Cytotoxicity; DNA - chemistry; DNA - drug effects; DNA/protein binding; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ferrocene; Ferrous Compounds - chemistry; Humans; Iridium - chemistry; Metallocenes; Molecular docking; Molecular Docking Simulation; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Pyridines - chemistry; Rhodium - chemistry; Ru(II)/Rh(III)/Ir(III) complexes; Ruthenium - chemistry; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - drug effects; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.06.052

Efficacy of the ferrocene appended piano-stool dipyrrinato complexes [(η6-C6H6)RuCl(fcdpm)] (1), [(η6-C10H14)RuCl(fcdpm)] (2), [(η6-C12H18)RuCl(fcdpm)] (3) [(η5-C5Me5)RhCl(fcdpm)] (4) and [(η5-C5Me5)IrCl(fcdpm)] (5) [fcdpm = 5-ferrocenyldipyrromethene] toward anticancer activity have been described. Binding of the complexes with calf thymus DNA (CT-DNA) and BSA (bovine serum albumin) have been thoroughly investigated by UV–Vis and fluorescence spectroscopy. Binding constants for 1–5 (range, 104–105 M−1) validated their efficient binding with CT-DNA. Molecular docking studies revealed interaction through minor groove of the DNA, on the other hand these also interact through hydrophobic residues of the protein, particularly cavity in the subdomain IIA. In vitro anticancer activity have been scrutinized by MTT assay, acridine orange/ethidium bromide (AO/EtBr) fluorescence staining, and DNA ladder (fragmentation) assay against Dalton's Lymphoma (DL) cells. Present study revealed that rhodium complex (4) is more effective relative to ruthenium (1–3) and iridium (5) complexes. Five heteroleptic Ru(II), Rh(III) and Ir(III) complexes containing ferrocene have been explored as anticancer agents. The binding behavior of these complexes with calf thymus DNA (CT-DNA) and BSA (bovine serum albumin) has been followed by UV–vis and fluorescence spectroscopy. To gain deep insight into the binding sites molecular docking studies have been carried out with DNA and HSA. Further, in vitro anticancer activities have been accessed by MTT assay, acridine orange/ethidium bromide (AO/EtBr) fluorescence staining, and DNA ladder (fragmentation) assay against Dalton's Lymphoma (DL) cells. [Display omitted] •Organometallic complexes having 5-fcdpm have been explored as anticancer agents.•Interactions with CT-DNA and BSA studied by UV–vis and fluorescence spectroscopy.•Molecular docking of 1–5 with DNA and HSA has been performed.•In vitro anticancer activities have been explored by various techniques.